P-gp Cancer Research Results

P-gp, permeability-glycoprotein: Click to Expand ⟱
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P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is a membrane protein that plays a crucial role in the transport of various substances across cellular membranes. It is part of the ATP-binding cassette (ABC) transporter family.
P-glycoprotein is often overexpressed in a variety of cancers, including breast cancer, lung cancer, leukemia, and ovarian cancer.

- The overexpression of P-glycoprotein (P-gp), is widely considered as an important reason for the MDR (multidrug resistance).
Scientific Papers found: Click to Expand⟱
5431- AG,    Advances in research on the anti-tumor mechanism of Astragalus polysaccharides
- Review, Var, NA
AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

5434- AG,    Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview
- Review, Liver, NA
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

557- ART/DHA,    Artemisinin and Its Derivatives in Cancer Care
- Review, Var, NA
*BioAv↓, with High fat and high calorie meals
*BioAv↑, DHA dihydroartemisinin have improved bioavailability
Apoptosis↑,
EGFR↓,
CD31↓,
Ki-67↓,
P53↓,
TfR1/CD71↑,
P-gp↓, many artemisinin derivatives act as P-gp inhibitors
PD-1↝, Caution when used with mmunotherapy (PD1/PDL1 inhibitors)

5497- Ba,    Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics
- Review, Var, NA
*Inflam↓, pharmacological effects of baicalin and baicalein, such as anti-inflammation, anti-cancer, and anti-pruritic effects, have been reported in the literature [
AntiCan↑,
BioAv↝, Baicalin is metabolized to baicalein by β-glucuronidase in the intestine [12], and this metabolic process is a critical stage for absorption of baicalin [6,12].
BioAv⇅, literature indicated that the kinds and numbers of intestinal microbiota in individuals might affect the pre-systemic metabolism and absorption process of baicalin in the intestine
BioAv↓, significantly reduced bioavailability of baicalin was obtained in antibiotic-pretreated rats when compared with normal rats.
CYP3A2↓, CYP3A inhibition P-gp inhibition
P-gp↓,

5250- Ba,    Exploring baicalein: A natural flavonoid for enhancing cancer prevention and treatment
- Review, Var, NA
Apoptosis↑, Baicalein is thought to prevent cancer progression by inducing apoptosis, autophagy, and genome instability, and its ability to promote chemo-potentiation, anti-metastatic effects, and regulate specific signalling molecules and transcription factors.
TumAuto↑,
DNAdam↑,
*antiOx↑, Baicalein has already been proven to be a radical scavenger that acts as an antioxidant [14,15
Inflam↓, it can also reduce inflammation [16] and act as an E2 prostaglandin inhibitor [17].
PGE2↓,
TumCCA↑, Baicalein properties prevent cell proliferation, induce apoptosis, autophagy, cell cycle arrest, cancer cell migration and invasion, and decrease angiogenesis [18,19].
TumCMig↓,
TumCI↓,
angioG↓,
selectivity↑, Furthermore, some studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells.
ChemoSen↑, the current review emphasises baicaleins' synergistic potential with other chemotherapeutic agents
HIF-1↓, baicalein against ovarian cancer by demonstrating that it can limit tumour cell viability by downregulating the expression of cancer-promoting genes such as HIF-1, cMyc, NFkB, and VEGF
cMyc↓,
NF-kB↓,
VEGF↓,
P53↑, Baicalein has been shown to activate p53, a tumour suppressor protein that regulates cell growth and division [26].
MMP2↓, anticancer properties of baicalein are mediated through various molecular mechanisms, including inhibition of MMP-2;
CSCs↓, inhibition of cancer stem cells
Bcl-xL↓, after bladder cancer cells were treated with baicalein, the expression of antiapoptotic genes (Bcl2, Bcl-xL, XIAP, and survivin) was reduced, and cell viability was decreased [38].
XIAP↓,
survivin↓,
tumCV↓,
Casp3↑, upregulating the expression of caspase-3 and caspase-8 and decreased the BCL-2/BAX ratio [16]
Casp8↑,
Bax:Bcl2↑,
Akt↓, in lung cancer cells, apoptosis was induced through the downregulation of the Akt/mTOR signalling pathway [25].
mTOR↓,
PCNA↓, baicalein treatment promoted apoptosis in mice with U87 gliomas by downregulating PCNA expression, enhancing the expression of caspase-3 and caspase-9 and improving the Bax/Bcl-2 ratio
MMP↓, baicalein treatment of lung cancer cells caused a collapse of the mitochondrial membrane potential (MMP), an increase in ROS generation, and enhanced PARP, caspase 3, and caspase 9 cleavage,
ROS↑,
PARP↑,
Casp9↑,
BioAv↑, Baicalein has been found to enhance the cytotoxicity and bioavailability of certain cancer therapy drugs when combined [85]
eff↑, combination of baicalein with silymarin differentially decreased the viability of HepG2 cells, enhanced the proportion of cells in the G0/G1 phase, upregulated tumour suppressors such as Rb and p53 and CDK inhibitors, and downregulated cyclin D1, cyc
P-gp↓, By inhibiting P-glycoprotein (P-gp), baicalein can increase the accumulation of chemotherapeutic drugs within cancer cells [21]
BioAv↑, selenium–baicalein nanoparticles as a targeted therapeutic strategy for NSCLC. This strategy significantly improves the bioavailability of baicalein through several mechanisms.
selectivity↑, ome studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells

2608- Ba,    Baicalein sensitizes hepatocellular carcinoma cells to 5-FU and Epirubicin by activating apoptosis and ameliorating P-glycoprotein activity
- in-vitro, HCC, Bel-7402
Apoptosis↑, Baicalein induced apoptosis and autophagy and decreased P-gp and Bcl-xl expression levels.
TumAuto↑,
P-gp↓,
Bcl-xL↓,
ChemoSen↑, We showed that Baicalein can reverse P-glycoprotein (P-gp)-mediated drug resistance.

2290- Ba,    Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer
- Review, GI, NA
p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC

5553- BBM,    A review on berbamine–a potential anticancer drug
- Review, Var, NA
P-gp↓, Treatment with berbamine decreased P-glycoprotein (P-gp) expression and down-regulated expression of MDR1 (multi-drug resistance1) and survivin mRNA in K562/A02 cells
MDR1↓,
survivin↓,
NF-kB↓, decrease expression of nuclear factor-B (NF-B), phosphoIB, IKK, and survivin.
TumCP↓, In a chronic myeloid leukemia cell line KU812, berbamine inhibited cell proliferation in a time- and dose-dependent manner, with IC50 values for treatments of 24, 48, and 72 h at 5.83, 3.43, and 0.75 μg/ml, respectively.
TumCCA↑, Berbamine induced cell cycle arrest at the G1 phase and also induced apoptosis.
Apoptosis↑,
SMAD3↑, The compound up-regulated transcriptions of Smad3 and p21, and increased protein levels of both total Smad3 and phosphorylated Smad3.
P21↑,
cycD1/CCND1↓, The protein levels of cyclin D1 and c-Myc were reduced.
cMyc↑,
Bcl-2↓, The levels of the anti-apoptotic proteins Bcl-2 and Bcl-xL were decreased, and the level of the pro-apoptotic protein Bax was increased.
Bcl-xL↓,
BAX↑,
CaMKII ↓, The compound has been shown to specifically bind to the ATP-binding pocket of calmodulin kinase (CAMK)II, inhibit its phosphorylation, and trigger apoptosis.
ChemoSen↑, Berbamine also significantly enhanced the activity of anticancer drugs like trichostatin A and celecoxib.
MMP2↓, EBB down-regulated the activities and mRNA levels of matrix metalloproteinases (MMP) 2 and 9, and up-regulated the mRNA levels of tissue inhibitor of metalloproteinases (TIMP) 1.
MMP9↓,
TIMP1↑,
cl‑Casp3↑, induction of apoptosis, including activation and cleavage of caspases 3, 8, 9 and PARP.
cl‑Casp9↑,
cl‑Casp8↑,
cl‑PARP↑,
IL6↓, BBD inhibited autocrine IL-6 production, and down-regulated membrane IL-6 receptor (IL-6R) expression.
ROS↑, Production of reactive oxygen species (ROS) was increased by BBMD3 in these cells.

5644- BCA,    Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways
- Review, Var, NA
P-gp↓, Biochanin A Inhibits P-gp mediated transport function.

5643- BCA,  GEN,  QC,  SIL,  KaempF  P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review
- in-vitro, NA, NA
P-gp↓, large number of flavonoids on P-gp inhibition. Biochanin-A, genistein, quercetin, chalcone, silymarin, phloretin, morin, and kaempferol

5642- BCA,    Interactions between the flavonoid biochanin A and P-glycoprotein substrates in rats: in vitro and in vivo
- vitro+vivo, Nor, NA
P-gp↓, Morin, phloretin, biochanin A, chalcone, and silymarin significantly increased DNM accumulation by greater than 2.5-fold, suggesting they are P-gp inhibitors.
BioAv↓, disconnect between the in vitro and in vivo data suggests that P-gp interactions mediated by biochanin A may be limited due to its poor bioavailability and rapid clearance

5640- BCA,    Improved effectiveness of biochanin A as a P-gp inhibitor in solid dispersion
- in-vitro, Nor, NA
*P-gp↓, In conclusion, SD formulation improved the in vivo effectiveness of biochanin A as a P-gp inhibitor
BioAv↑, In order to solubilize poorly water soluble drugs, formulation of solid dispersions (SD) with hydrophilic carriers has been demonstrated as a promising technique
other↝, P-gp inhibitiors should play an important role in relieving MDR in anticancer treatment and also enhancing the bioavailability of various drugs acting as P-gp substrates.
other↑, SD formulation with the mixture of Solutol ® HS15 and HPMC 2910 should be effective to improve the solubility and dissolution of biochanin A.

3697- BM,    Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies
- Review, AD, NA
*ROS↓, Numerous studies suggested that B monnieri’s bioactive components (ie, bacosides) protect the brain against oxidative damage and age-related cognitive deterioration with several mechanisms of action
*cognitive↑, patients who took 300 mg of Bacognize orally twice a day showed a statistically significant improvement in various components of Mini-Mental State Examination Scale (MMSES)
*memory↑, (BME)-treated rat serum and could directly or indirectly interact with the neurotransmitter systems to improve memory and learning ability
*BBB↑, Bacosides present in B monnieri are commonly nonpolar glycosides,27 which enable it to cross the blood-brain barrier (BBB) via simple lipid-mediated passive diffusion.
*P-gp↓, The results showed that B. monnieri downregulated both intestinal Pgp and CYP3A expression levels, depending on the testosterone hydroxylase catalytic activity in liver and intestine
*CYP3A2↓,

5649- BNL,    Borneol, a novel agent that improves central nervous system drug delivery by enhancing blood–brain barrier permeability
- Review, Nor, NA
*BBB↑, A growing body of evidence confirms that the ‘orifice-opening’ effect of borneol is principally derived from opening the BBB. Borneol is therefore believed to be an effective adjuvant that can improve drug delivery to the brain
*other↑, Borneol also protects the structural integrity of the BBB against pathological damage.
*P-gp↓, Both in vitro and in vivo studies have shown that borneol inhibited the expression of P-gp and other ABC transporters,
*toxicity⇅, Natural borneol has been extensively used in aromatherapy and in natural and cosmetic products because of its low toxicity compared to synthetic borneol, which toxicity is relatively high as it degrades slowly during storage, and noxious camphor
*BioAv⇅, In mice, a single oral dose of borneol accumulates in organs in the order of liver > brain > kidney > heart > spleen > muscle > lung, which confirms its considerably higher bioavailability in the brain than in most other organs
*Dose↑, Intranasal drug delivery can avoid gastrointestinal destruction and hepatic first-pass metabolism, resulting in rapid onset of effect and high brain bioavailability.
*ABC↓, Both in vitro and in vivo studies have shown that borneol inhibited the expression of P-gp and other ABC transporters,
*MRP1↓, including multidrug resistance protein 1 (Mrp1), 1a (Mdr1a) and 1 b (Mdr1b),
*5HT↑, systemic borneol was found to increase the levels of histamine and serotonin in the hypothalamus
*GABA↑, and levels of l-aspartic acid, glutamate, glycine and γ-aminobutyric acid (GABA) in the corpus striatum of rats (Zhang et al., 2012).
*eff↑, Co-incubation with borneol increased the uptake of Huperzine A loaded aprotinin-modified nanoparticles by capillary endothelial cells

5650- BNL,    Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model
- in-vivo, Nor, NA
*P-gp↓, Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression.
*NF-kB↑, Borneol could activate nuclear factor-κB (NF-κB)
*eff↓, inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol.
*Dose↝, Moreover, 10 μg/mL and 20 μg/mL borneol treatment decreased P-gp expression in BMECs, the reduction of P-gp expression were 27% and 58% compared to control group respectively at 4 h after treatment

5656- BNL,    Role of borneol as enhancer in drug formulation: A review
- Review, Nor, NA - Review, Stroke, NA - Review, AD, NA
*eff↑, borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times.
BBB↑, Given its ability to enhance cross-barrier permeation
ChemoSen↑, interest in borneol, for various purposes, including anti-inflammatory, analgesic, neuronal protection, permeability promotion, chemotherapy sensitization and borneol-modified nano-drug delivery system
*Inflam↓, borneol and its synthetic counterpart exhibit noteworthy anti-inflammatory properties by reducing inflammatory factors, namely NO, TNF-α, and IL-6
*NO↓,
*TNF-α↓,
*IL6↓,
*Bacteria↓, Borneol has shown exceptional anti-bacterial effect activity and has been coupled in TCM formulas for external use against bacteria growth
*eff↑, Studies indicated that the combined administration of edaravone and borneol (i.e. Edaravone Dexborneol) exhibited synergistic effects in the treatment of ischemic stroke
*Aβ↓, efficient prohibition of the accumulation of Aβ in the brain
*SOD↑, Borneol has been reported to exhibit exceptional potential in the augmentation of superoxide dismutase (SOD) activity
*neuroP↑, Both naturally occurring and artificially synthesized borneol exhibited neuroprotective properties
*EPR↑, The permeation-enhancing effects of natural borneol and synthetic borneol on various drug properties have been observed,
toxicity↓, Borneol is an ideal absorption enhancer with low toxicity, little stimulation to gastrointestinal mucosa and strong permeability
P-gp↓, The inhibition of P-gp expression has been observed as a potential mechanism for reversing multidrug resistance, with borneol implicated in this process
eff↑, Research findings indicated that natural borneol can substantially enhance the anticancer properties of paclitaxel and curcumin.
other↝, specifically, the incorporation of borneol has been associated with improvements in drug solubility, enhanced cellular uptake, reduced organ toxicity, and mitigation of multiple drug resistances.

5659- BNL,    Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood–brain barrier permeability: a preclinical systematic review and meta-analysis
- Review, Var, NA
BBB↑, borneol up-regulated BBB permeability
P-gp↓, inhibition of drug efflux through combining with P-gp competitively and inhibiting its activity
MDR1↓, decreasing the expressions of both Mdr1a, Mdr1b, and Mrp1 in hippocampus and hypothalamus
HIST1H3B?,

5660- BNL,    Recent Progress on the Synergistic Antitumor Effect of a Borneol-Modified Nanocarrier Drug Delivery System
- Review, Var, NA
TumMeta↓, We focus on the updated works of improving therapeutic efficacy, reducing toxicity, inhibiting tumor metastasis, reversing multidrug resistance, and enhancing brain targeting
BBB↑,
EPR↑, Nanocarriers can increase the concentration of a drug at the tumor site via the enhanced permeability and retention (EPR) effect, which also reduces systemic toxicity
toxicity↓,
BioAv↑, Moreover, borneol can promote the transdermal absorption of other drugs and increase their blood concentration and bioavailability
ChemoSen↑, application of borneol in nanocarriers has great potential to improve the targeting and enhance the accumulation of chemotherapeutic drugs in tumors.
eff↑, Borneol enhanced the antidepressant effects of asiaticoside by promoting its penetration of the BBB, thus enhancing the anti-depressant effects with enhanced 5-HT and BDNF, and reduced TNF-α levels
other↑, Borneol enhanced the antidepressant effects of asiaticoside by promoting its penetration of the BBB, thus enhancing the anti-depressant effects with enhanced 5-HT and BDNF, and reduced TNF-α levels
P-gp↓, inhibition of the function and expression of P-gp
MDR1↓, borneol could significantly inhibit the activity of drug resistance proteins such as multidrug resistance mutation 1 (MDR1) and P-gp and accelerate the transportation of drugs
ROS↑, chemotherapeutic sensitizer works along with the chemotherapeutic drugs to promote anticancer effect by increasing the level of reactive oxygen species (ROS) (119), arresting cell cycle (120)
TumCCA↑,
other↝, volatility of borneol makes it extremely unstable during preparation and storage.
BioAv↓, the poor water solubility of NB is not conducive to blood circulation, which greatly limits the effective delivery to the treatment site and greatly reduces its therapeutic effect.
DNAdam↑, lead to the activation of signaling pathways, including those involved in ROS, DNA damage, and apoptosis
BioEnh↑,

5663- BNL,    Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice
- in-vivo, AD, NA
*ZO-1↓, Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression
*cl‑Casp3↓, Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio
*Bax:Bcl2↓,
*MDA↓, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice
*Apoptosis↓,
*Aβ↓,
*BACE↓,
*cognitive↑,
*BioAv↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
memory↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
P-gp↓, This may be caused by a higher dose of BO inhibiting the action of the P-gp transporter in intestinal mucosa and CYP450 metabolism in the liver.
BioEnh↑,

5666- BNL,    Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider
- in-vivo, AD, NA
*BioAv↑, Compared to intravenous injection, improved brain targeting effect was observed by intranasal route
*eff↑, After VIN—NE intranasal administration, the plasma absolute bioavailability reached 86%, while the oral bioavailability of VIN is just 6.7%
*Dose↝, when the dosage of BOR was 1 mg/kg, the best brain targeting effect could be achieved.
*P-gp↓, Additionally, it has been demonstrated that nanoemulsion may inhibit P-gp efflux pump
*BBB↑, BOR as a brain distribution inducer could help drug transport from plasma into brain through enhancing BBB permeability
*NF-kB↓, BOR could increase BBB permeability by inhibiting nuclear factor κB (NF-κB), down-regulating P-gp and then decreasing efflux [32].
*IL1β↓, On the contrary, BOR can inhibit the expression of interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9) [34,35],
*MMP9↓,

5669- BNL,    Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol
- Review, Nor, NA - Review, AD, NA - Review, Stroke, NA
*eff↑, L-borneol has better potential in cerebrovascular diseases.
*eff↑, D-borneol exhibits better antitumour sensitizing effects than L-borneol.
*toxicity↝, Synthetic borneol is less safe. Synthetic borneol is widely used because of its advantages of low cost and easy availability.
*Inflam↓, It has anti-inflammatory, analgesic, antipyretic, antibacterial, neuroprotective, and permeation-promoting effects.
*Bacteria↓,
*neuroP↑,
*Half-Life↝, oral administration. It reaches its highest concentration in 30 min, and its half-life is 18 h
*BBB↑, and can easily pass through the BBB and blood–ocular barrier (BOB).
*BioEnh↑, Borneol can promote the absorption and affect the distribution of other drugs, which is beneficial for reducing the dosage, prolonging the action time, and improving the curative effects of these drugs
*P-gp↓, inhibitory activity against P-gp is as follows: L-borneol > D-borneol ≈ synthetic borneol.
*CYP3A4↓, inhibition of intestinal CYP3A4 would improve the bioavailability of drugs.
*ROS↓, and reduce the rate of cerebral oedema and the volume of infarcts by inhibiting oxidative stress
*neuroP↑, neuroprotective effects of the three kinds of borneol are as follows: L-borneol > synthetic borneol > D-borneol

5851- CAP,    Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells
- in-vitro, Oral, NA
ChemoSen↑, The ability of capsaicin co-treatment to sensitize cancer cells to anticancer drugs has been widely documented,
TumAuto↑, capsaicin sensitizes oral cancer cells to anticancer drugs through the up-regulation of autophagy and down-regulation of ribophorin II
ER Stress↑, Capsaicin Enhances ER Stress and Autophagy
P-gp↓, These findings indicated that capsaicin may inhibit P-glycoprotein to potentiate the anticancer effects of chemotherapeutics.

5850- CAP,    Anticancer Activity of Natural and Synthetic Capsaicin Analogs
- Review, Var, NA
TRPV1↑, Capsaicin functions as a classic agonist of the TRPV1 receptor
Ca+2↑, multiple mechanisms such as increase of intracellular calcium, induction of calpain activity, reactive oxygen species (ROS) generation, inhibition of coenzyme Q, suppression of mitochondrial respiration,
ROS↑,
mitResp↓,
ChemoSen↑, capsaicin promotes the apoptotic activity of cancer chemotherapy agents by multiple mechanisms
P-gp↓, capsaicin has been reported to inhibit p-glycoprotein efflux transporters in KB-C2 human endocervical adenocarcinoma cells.

5847- CAP,    An updated review on molecular mechanisms underlying the anticancer effects of capsaicin
- in-vitro, Liver, HepG2
HO-1↑, capsaicin induced the expression of HO-1 in human hepatoma HepG2 cells through the generation of ROS and subsequent activation of a redox-sensitive transcription factor nuclear factor erythroid related factor-2 (Nrf2)
ROS↑,
NRF2↑,
*lipid-P↓, capsaicin inhibits lipid peroxidation by increasing the activity of a battery of antioxidant enzymes
*SOD↑, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR)
*Catalase↑,
*GPx↑,
*GSR↑,
*PGE2↓, inhibitory effects of capsaicin on the production of prostaglandin E2 (PGE2) in macrophages incubated with LPS or TPA (
*COX2↓, the inhibition of COX-2 and iNOS expression by capsaicin in these cells is mediated in a VR1/TRPV1-independent manner
*iNOS↓,
TumCP↓, anticancer effects of capsaicin are partly mediated through the inhibition of cancer cell proliferation.
TumCCA↑, Capsaicin inhibited the growth of human esophageal epidermoid carcinoma (CE 81T/VGH) cells by arresting the cell cycle at the G1 phase through the downregulation of cyclin E, cyclin dependent kinase (Cdk)-4 and -6,
cycE/CCNE↓,
CDK4↓,
MMP↓, Similarly, the inhibition of Cdk-2,-4 and-6, the generation of ROS, and the loss of mitochondrial membrane potential were associated with reduced proliferation of human bladder cancer cells upon capsaicin treatment
P53↑, capsaicin is mediated through the induction of p53 nd its target gene products such as, p21, and Bax.
P21↑,
BAX↑,
SIRT1↑, The same study also demonstrated that capsaicin induced autophagy in human fetal lung cells by inducing SIRT1
angioG↓, Capsaicin inhibited angiogenesis in the chick chorioallantoic membrane
P-gp↓, Capsaicin inhibited the P-gp activity in human intestinal carcinoma (Caco2) cells in a concentration- and time-dependent manner (
ChemoSen↑, Capsaicin exhibited synergistic growth inhibitory effects with 5-fluorouracil (5FU) in cholangiocarcinoma cells in culture as well as xenograft tumor growth in nude mice

5212- CAP,  PI,  Chemo,    Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to Doxorubicin
- in-vitro, Colon, Caco-2
ChemoSen↑, Capsaicin and piperine synergistically enhanced the cytotoxicity of doxorubicin in Caco-2 and CEM/ADR 5000 cells.
P-gp↓, Capsaicin and Piperine Inhibited the Activity of P-gp
eff↑, piperine had a notable reversal effect in P-gp overexpressing cell lines, Caco-2 and CEM/ADR 5000

5765- CAPE,    Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats
- vitro+vivo, Colon, Caco-2
P-gp↓, CAPE and CAPE-NO2 increased the P-gp levels by 2.1- and 1.7-fold, respectively.

5965- CEL,  Cisplatin,    Celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma via PI3K/Akt pathway
- in-vitro, OS, MG63
COX2↓, celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt.
ChemoSen↑, It has been confirmed that celecoxib enhances apoptosis and cytotoxic effect of cisplatin
MDR1↓, MDR1, MRP1, BCRP and Trkb, E-cadherin, β-catenin were significantly downregulated in cells treated with the combination of celecoxib and cisplatin
MRP1↓,
E-cadherin↓,
β-catenin/ZEB1↓,
Apoptosis↑, Down-regulation of MDR1, MRP1 and BCRP correlated with increased apoptosis
TumCCA↑, celecoxib caused G1 phase arrest and significantly inhibited cell growth,
TumCG↓,
P-gp↓, COX-inhibitors may sensitize cancer cells to chemotherapeutic drugs via inhibiting P-gp, MRP1 and BCRP, and enhance the effect of anticancer drugs
PI3K↓, COX-2 inhibitors are known to inhibit the PI3K/Akt pathway
Akt↓,

441- CUR,    Curcumin Regulates ERCC1 Expression and Enhances Oxaliplatin Sensitivity in Resistant Colorectal Cancer Cells through Its Effects on miR-409-3p
- in-vitro, CRC, HCT116
ERCC1↓,
Bcl-2↓,
GSTP1/GSTπ↓,
MRP↓,
P-gp↓,
miR-409-3p↑,
survivin↓,

4914- DSF,  immuno,    Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies
- Review, Var, NA
AntiTum↑, potential as an anti-tumor agent and even as an enhancer of cancer immunotherapy
eff↑, Targeted delivery: through nanotechnology, specific delivery of disulfiram to tumor sites can be achieved to minimize damage to normal tissues and increase drug accumulation in tumor cells
ALDH↓, It works by inhibiting an enzyme called Aldehyde Dehydrogenase (ALDH).
Dose↝, DSF is not only affordable at $20–40 for a daily dose of 250 mg taken orally in the USA, but it is also considered to be safe, allowing for long-term treatment at the same dosage.
RadioS↑, DSF/Cu can enhance the effects of ionizing radiation and induce ICD in breast cancer
angioG↓, inhibition of angiogenesis and metastasis, make it a versatile agent in combating cancer
TumMeta↓,
BioAv↝, limitations associated with its delivery, solubility, and off-target toxicity have prompted the development of innovative strategies to improve its clinical efficacy
ROS↑, DSF effectively treats tumors. Such as increasing the production of ROS, causing DNA damage, and impeding enzyme activity.
DNAdam↑,
P-gp↓, DSF can target P-glycoprotein (P-gp) dysfunction, cancer stem cells (CSCs), and hinder the process of epithelial-mesenchymal transition (EMT).
CSCs↓,
EMT↓,
Imm↑, DSF stimulates the immune system
SOD↓, generation of ROS, inhibition of the superoxide dismutase activity and activation of the mitogen-activated protein kinase (MAPK)
MAPK↓,
NF-kB↓, NF-κB inhibiting activity of DSF could be attributed to their inhibition of the proteasome and degradation other regulatory redox-sensitive proteins.
ChemoSen↑, therapeutic effect of combining DSF with conventional cancer drugs like cisplatin and doxorubicin (DOX) has been proven to be enhanced.
eff↑, combination use of DSF with immunotherapy has shown remarkable success in preclinical and clinical studies.
toxicity↝, The administration of disulfiram necessitates the complete abstinence from alcohol
BioAv↑, researchers use lipid nanoparticles as carriers for disulfiram and used to improve its bioavailability and reduce side effects.
*Inflam↓, DSF has the ability to inhibit inflammation, which has potential applications in treating various inflammatory diseases,
Sepsis↓, Mice with sepsis experienced reduced mortality when administered with DSF-loaded lactoferrin nanoparticles,

5013- DSF,  Cu,  Z,    Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease
- vitro+vivo, Melanoma, NA - Case Report, Melanoma, NA
P-gp↓, disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-κB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice.
NF-kB↓,
ChemoSen↑,
angioG↓,
TumCG↓,
TumMeta↓, The combination of oral zinc gluconate and disulfiram at currently approved doses for alcoholism also induced >50% reduction in hepatic metastases and produced clinical remission in a patient with stage IV metastatic ocular melanoma, who has continu
Remission↑,
toxicity↓, who has continued on oral zinc gluconate and disulfiram therapy for 53 continuous months with negligible side effects.
ATF2↓, Disulfiram and Metals Inhibit ATF/CREB DNA Binding and Cyclin A Expression
CREB↓,
cycA1/CCNA1↓,
TumCG↓, Disulfiram and Zn2+ Inhibit Melanoma Growth and Angiogenesis in Mice
angioG↓,
Dose↝, 250 mg/d disulfiram with the largest meal of the day. This dose was increased to 500 mg/d after 1 month. Zinc gluconate (50 mg chelated elemental Zn2+, ) was also given thrice daily but not concurrent with disulfiram administration.
toxicity↝, On starting the protocol, the patient suffered grade 1 (National Cancer Institute Common Toxicity Criteria, version 2.0) diarrhea, nausea, depression, and malaise. Except for nausea, these side effects resolved within 2 months of continued treatment.

2992- EGCG,    Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity
- Review, Var, NA
AP-1↓, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species
Sp1/3/4↓,
NF-kB↓,
ERK↓, EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression.
P-gp↓,
HSP27↓,
β-catenin/ZEB1↓,
MMPs↓,
TNF-α↓, suppress the production of inflammatory cytokines such as TNFα and IL-1β.
IL1β↓,
MMP2↓, EGCG inhibited MMP2 secretion in glioblastoma cells.

2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
ROS↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
cl‑Casp3↑,
Cyt‑c↑, leading to cytochrome-c release
lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
TumCMig↓,
TumCI↓,
uPA↓,
ERK↓,
MMP9↓,
NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
cFos↓,
cJun↓,
AP-1↓,
TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
mTORC2↓,
TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
TGF-β↓,
EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
Akt↓,
mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
IRE1↑,
ATF4↑,
GRP78/BiP↑,
ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
cycE/CCNE↓,
cycD1/CCND1↓,
P21↑,
COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
Wnt↓,
EGFR↓,
β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
TCF-4↓,
MMP7↓,
RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells

5152- GamB,    Gambogic Acid as a Candidate for Cancer Therapy: A Review
- Review, Var, NA
AntiCan↑, GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumCI↓,
TumMeta↓,
angioG↓,
eff↑, In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers
NF-kB↓, GA could inhibit the activation of NF-κB
P53↑, GA increases p53 expression via down-regulating MDM2 in wild type p53 expressing human cancer cells (non-small cell lung H1299)
P21↑, GA could enhance p21Waf1/CIP1 expression to induce cell apoptosis in human breast cancer cells (MCF-7) via suppressing MDM2
MDM2↓,
HSP90↓, GA was considered as a natural product inhibitor of Hsp90
Bcl-2↓, bcl-2 reduction is associated with the release of cytochrome c, leading to an apoptosis cascade reaction
Cyt‑c↑,
Casp↑,
MMP↓, rapid mitochondrial membrane depolarization and fragmentation
Casp3↑, activation of caspase-3, 9 and cleaved PARP and increased ratio of bax/bcl-2.
Casp9↑,
cl‑PARP↑,
Bax:Bcl2↑,
ROS↑, GA-induced reactive oxygen species (ROS) may be the cause of the collapse of mitochondrial transmembrane potential, which could also down-regulate SIRT1 in multiple myeloma
SIRT1↓,
TrxR1↓, GA may also interact with the thioredoxin reductase 1 (TrxR1) to elicit oxidative stress leading to ROS accumulation in hepatocellular carcinoma
Fas↓, GA with increased death receptor (Fas, FasL, Fas-associated protein with death domain (FADD) and Apaf-1) and deoxyribonucleic acid (DNA) fragmentation.
FasL↑,
FADD↑,
APAF1↑,
DNAdam↑,
NF-kB↓, GA could inhibit NF-κB pathway through suppressing IκBα and p65 phosphorylation
STAT3↓, GA also suppressed the signal transducer and activator of transcription (STAT3) phosphorylation to induce cell apoptosis
MAPK↓, GA induced cell apoptosis via suppression of mitogen-activated protein kinases (MAPK) pathway and c-fos
cFos↓,
EGFR↓, GA could also enhance epidermal growth factor receptor (EGFR) degradation and inhibit AKT/mTOR complex 1 (mTORC1) via up-regulating AMP-activated protein kinase (AMPK)-
Akt↓,
mTOR↓,
AMPK↑,
TumCCA↑, GA could obviously induce G2/M or G0/G1 arrest in various cancer cell lines, such as MCF-7 cells, K562 cells, U2OS cells, and so on
ChemoSen↑, GA distinctly sensitized doxorubicin (DOX)-resistant breast cancer cells through inhibiting P-glycoprotein and suppressing the survivin expression revealed by ROS-mediated activation of the p38 MAPK
P-gp↓,
survivin↓,

1972- GamB,  doxoR,    Gambogic acid sensitizes resistant breast cancer cells to doxorubicin through inhibiting P-glycoprotein and suppressing survivin expression
- in-vitro, BC, NA
eff↑, we found that GA can markedly sensitize doxorubicin (DOX)-resistant breast cancer cells to DOX-mediated cell death
P-gp↓, GA increased the intracellular accumulation of DOX by inhibiting both P-gp expression and activity
ROS↑, combination effect was associated with the generation of intracellular reactive oxygen species (ROS)
survivin↓, and the suppression of anti-apoptotic protein survivin
p38↑, ROS-mediated activation of p38 MAPK was revealed in GA-mediated suppression of survivin expression

2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
*P-gp↓, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6),
*ROS↓,
*TNF-α↓,
*IL10↓,
*IL6↓,
eIF2α↑, Bcl-2, phosphorylated eIF2α, CHOP,GRP78, Bax, cleaved caspase-9 and phosphorylated PERK
CHOP↑,
GRP78/BiP↑,
BAX↑,
cl‑Casp9↑,
p‑PERK↑,
ER Stress↑, endoplasmic reticulum stress and proteins in apoptosis in 95-D and A549 cells
Apoptosis↑,
MMPs↓, decrease in levels of matrix metal-mloproteinases, P-glycoprotein expression, the formation of mammosphere, H3K27 methyltransferase, c-FLIP, level of CXCR4 receptor,pluripotency-factors, Twist-1, class I histone deacetylases, steroid receptor co
cFLIP↓,
CXCR4↓,
Twist↓,
HDAC↓,
BMPs↑, enhancement in Bax protein, and (BMP7), as well as interference with an activator of transcription 3 (STAT3), (mTOR), (EGFR), (NF-kB) and Shh
p‑STAT3↓, secreased the phosphorylation of STAT3
mTOR↓,
EGFR↓,
NF-kB↓,
Shh↓,
VEGF↓, induce apoptosis, and regulate the vascular endothelial growth factor-A expression (VEGF-A)
tumCV↓, human glioma cell lines (U251 and U-87 MG) through inhibition of colony formation, glioma cell viability, cell migration, invasion, suppression of ERK and AKT signalling cascades, apoptosis induction, and reduction of Bcl-2 expression.
TumCMig↓,
TumCI↓,
ERK↓,
Akt↓,
Bcl-2↓,
Nestin↓, increased the Bax expression, lowered the CD133, EGFR, and Nesti
CD133↓,
p‑cMET↑, HKL through the downregulating the phosphorylation of c-Met phosphorylation and stimulation of Ras,
RAS↑,
chemoP↑, Cheng and coworker determined the chemopreventive role of HKL against the proliferation of renal cell carcinoma (RCC) 786‑0 cells through multiple mechanism
*NRF2↑, , HKL also effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in in vivo and in vitro model
*NADPH↓, (HUVECs) such as inhibition of NADPH oxidase activity, suppression of p22 (phox) protein expression, Rac-1 phosphorylation, reactive oxygen species production, inhibition of degradation of Ikappa-B-alpha, and suppression of activity of of NF-kB
*p‑Rac1↓,
*ROS↓,
*IKKα↑,
*NF-kB↓,
*COX2↓, Furthermore, HKL treatment the inhibited cyclooxygenase (COX-2) upregulation, reduces prostaglandin E2 production, enhanced caspase-3 activity reduction
*PGE2↓,
*Casp3↓,
*hepatoP↑, compound also displayed hepatoprotective action against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 liver cells in in vitro model
*antiOx↑, compound reduces the level of acetylation on SOD2 to stimulate its antioxidative action, which results in reduced reactive oxygen species aggregation in AML12 cells
*GSH↑, HKL prevents oxidative damage induced by H2O2 via elevating antioxidant enzymes levels which includes glutathione and catalase and promotes translocation and activation transcription factor Nrf2
*Catalase↑,
*RenoP↑, imilarly, the compound protects renal reperfusion/i-schemia injury (IRI) in adult male albino Wistar rats via reducing theactivities of serum alkaline phosphatase (ALP), aspartate aminotrans- ferase (AST) and alanine aminotransferase (ALT)
*ALP↓,
*AST↓,
*ALAT↓,
*neuroP↑, Several reports and works have shown that HKL displays some neuroprotective properties
*cardioP↑, Cardioprotection
*HO-1↑, the expression level of heme oxygenase-1 (HO-1)was remarkably up-regulated and miR-218-5p was significantly down-regulated in septic mice treated with HKL
*Inflam↓, anti-inflammatory action of HKL at dose of 10 mg/kg in the muscle layer of mice

2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp↓, The expres- sion of P-gp at mRNA and protein levels is reduced in HNK treatment on human MDR and MCF-7/ADR breast cancer cell lines

2179- itraC,    Repurposing itraconazole for the treatment of cancer
- Review, Var, NA
HH↓, Figure 1
angioG↓,
TumCCA↑,
MDR1↓,
P-gp↓,
mTOR↓,
VEGF↓,
Smo↓,
Gli1↓,
OS↑, Itraconazole 400 mg daily was administered over 4 days every 2 weeks. A response rate of 44% was achieved, with a higher median overall survival time (1,047 days) compared with that previously reported in other studies, which ranged between 7-10mts
PSA↓, After the patient declined castration treatment, itraconazole was administered and the PSA level reduced by >50% in 3 months (300 mg twice daily)

3464- MF,    Progressive Study on the Non-thermal Effects of Magnetic Field Therapy in Oncology
- Review, Var, NA
AntiTum↑, frequency below 300 Hz) exert anti-tumor function, independent of thermal effects
TumCG↓, Magnetic fields (MFs) could inhibit cell growth and proliferation; induce cell cycle arrest, apoptosis, autophagy, and differentiation; regulate the immune system; and suppress angiogenesis and metastasis via various signaling pathways
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Diff↑,
angioG↓,
TumMeta↓,
EPR↑, MFs not only promote the absorption of chemotherapy drugs by producing small holes on the surface of cell membrane
ChemoSen↑,
ROS↑, MF treatment has been shown to promote the generation of ROS in many studies (31, 71, 72), with exposure within a 60 Hz sinusoidal MF for 48 h in induced human prostate cancer for DU145, PC3, and LNCaP apoptoses
DNAdam↑, Repetitive exposure to LF-MFs induced DNA damage and accumulation of DSBs and triggered apoptosis in Hela and MCF7 cell lines
P53↑, PMFs could trigger apoptosis cell death by upregulating the p53 level and through the mitochondrial-dependent pathway
Akt↓, LF-MFs (300 mT, 6 Hz, 24 h) also induced apoptosis by suppressing protein kinase B (Akt) signaling, activating p38 mitogen-activated protein kinase (MAPK) signaling, and caspase-9, which is the executor of the mitochondrial apoptosis pathway
MAPK↑,
Casp9↑,
VEGFR2↓, reducing the expression and activation levels of VEGFR2
P-gp↓, A combination with the SMF (8.8 m T, 12 h) decreased the expression of P-glycoprotein (P-gp) in K562 cancer cells, while adriamycin itself induced an increase

5241- MF,    A review on the use of magnetic fields and ultrasound for non-invasive cancer treatment
- Review, Var, NA
other↑, Magnetic fields have been found to stimulate collagen density in and around the joints, and help to trigger Ca2+ flow to the defect site resulting in faster bone healing
BloodF↑, blood microcirculation revealed that magnetic fields have strong influence on relaxation and constriction of capillary blood vessels which alters the blood flow.
Glycolysis↓, In general, the glycolysis and glucose oxidations are decreased in diabetic patients leading to lower ATP production.
ATP↓,
VEGF↓, Application of magnetic fields can significantly decrease VEGF level and therefore reduces the growth and distribution of cancer to other parts of the body
ROS↑, SMF interacts with the charged molecules (ions, proteins etc.) of biological system through several physical mechanisms and alters the activity, concentration, and life time of paramagnetic free radicals i.e. ROS (reactive oxygen species),
P-gp↓, study demonstrated that 8.8 mT SMF enhances cytotoxic potency of Adriamycin on K562 cells due to decrease in the P-gp expression
Apoptosis↑, n vitro analysis in terms of apoptosis and cell electrical properties showed that MCF7 cells are highly reactive to 3 mT flux density and normal cells (MCF10) are unaffected.
selectivity↑,
Ca+2↑, Long PMF (50 Hz, 0.1–1 mT) for 7 days Undifferentiated PC12, increased intracellular Ca+ concentration and Catalase activity.
Catalase↑,

1807- NarG,    A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies
- Review, NA, NA
AntiTum↑, antitumor ability of naringin
TumCP↓,
tumCV↓,
TumCCA↑,
Mcl-1↓,
RAS↓,
e-Raf↓, suppressing the Ras/Raf/extracellular
VEGF↓,
AntiAg↑,
MMP2↓,
MMP9↓,
TIMP2↑,
TIMP1↑,
p38↓,
Wnt↓,
β-catenin/ZEB1↑,
Casp↑,
P53↑,
BAX↑,
COX2↓,
GLO-I↓,
CYP1A1↑,
lipid-P↓,
p‑Akt↓,
p‑mTOR↓,
VCAM-1↓,
P-gp↓,
survivin↓,
Bcl-2↓,
ROS↑, ↑oxidative stress, Prostate DU145 cell line 50–250 μM
ROS↑, ↑ROS, Stomach (Gastric) AGS cell line, 1–3 mM
MAPK↑,
STAT3↓,
chemoP↑, flavonoids have excellent radical scavenging and iron-chelating properties (Kaiserová et al., 2007), and they can act as an effective modulator for DOX-induced toxicity

1802- NarG,  ATV,    Bioenhancing effects of naringin on atorvastatin
- in-vivo, Nor, NA
BioEnh↑, a natural bioenhancer and reported to enhance the bioavailability of drugs by inhibiting cytochrome P450 and P-glycoprotein (P-gp)
LDL↓, Animals received AST along with naringin (15 and 30 mg/kg) shown higher percent reduction in both cholesterol and triglycerides levels
P450↓,
P-gp↓,

4949- PEITC,    Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells
- in-vitro, Cerv, HeLa
ROS↑, Cruciferous vegetable-derived phenethyl isothiocyanate (PEITC) selectively induces reactive oxygen species (ROS), leading to apoptosis of cancer cells, but not healthy cells.
selectivity↑,
CSCs↓, PEITC treatments resulted in a reduced number of ALDHhi hCSCs in a concentration-dependent manner
Sp1/3/4↓, PEITC suppressed the cancer-associated transcription factor (Sp1) and a downstream multidrug resistance protein (P-glycoprotein)
P-gp↓,
ALDH↓, PEITC inhibits ALDH2 in the liver
GSH↓, The electrophilic property of PEITC has been shown to covalently interact with nucleophilic glutathione (GSH), leading to ROS-induction in cells
TumCP↓, Phenethyl Isothiocyanate Treatment Suppressed HeLa Cancer Stem Cells Proliferation and Increased Early Apoptosis
Apoptosis↑,

2946- PL,    Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent
- Review, Var, NA
ROS↑, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cycD
GSH↓, reduced glutathione (GSH) levels in mouse colon cancer cells
DNAdam↑,
ChemoSen↑, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy
RadioS↑, piperlongumine treatment enhances ROS production via decreasing GSH levels and causing thioredoxin reductase inhibition
BioEnh↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine
selectivity↑, It shows selectivity toward human cancer cells over normal cells and has minimal side effects
BioAv↓, ts low aqueous solubility affects its anti-cancer activity by limiting its bioavailability during oral administration
eff↑, encapsulation of piperlongumine in another biocompatible natural polymer, chitosan, has been found to result in pH-dependent piperlongumine release and to enhance cytotoxicity via efficient intracellular ROS accumulation against human gastric carcin
p‑Akt↓, Fig 2
mTOR↓,
GSK‐3β↓,
β-catenin/ZEB1↓,
HK2↓, iperlongumine treatment decreases cell proliferation, single-cell colony-formation ability, and HK2-mediated glycolysis in NSCLC cells via inhibiting the interaction between HK2 and voltage-dependent anion channel 1 (VDAC1)
Glycolysis↓,
Cyt‑c↑,
Casp9↑,
Casp3↑,
Casp7↑,
cl‑PARP↑,
TrxR↓, piperlongumine (4 or 12 mg/kg/day for 15 days) administration significantly inhibits increase in tumor weight and volume with less TrxR1 activity in SGC-7901 cell
ER Stress↑,
ATF4↝,
CHOP↑, activating the downstream ER-MAPK-C/EBP homologous protein (CHOP) signaling pathway
Prx4↑, piperlongumine kills high-grade glioma cells via oxidative inactivation of PRDX4 mediated ROS induction, thereby inducing intracellular ER stress
NF-kB↓, piperlongumine treatment (2.5–5 mg/ kg body weight) decreases the growth of lung tumors via inhibition of NF-κB
cycD1/CCND1↓, decreases expression of cyclin D1, cyclin- dependent kinase (CDK)-4, CDK-6, p- retinoblastoma (p-Rb)
CDK4↓,
CDK6↓,
p‑RB1↓,
RAS↓, piperlongumine downregulates the expression of Ras protein
cMyc↓, inhibiting the activity of other related proteins, such as Akt/NF-κB, c-Myc, and cyclin D1 in DMH + DSS induced colon tumor cells
TumCCA↑, by arresting colon tumor cells in the G2/M phase of the cell cycle
selectivity↑, hows more selective cytotoxicity against human breast cancer MCF-7 cells than human breast epithelial MCF-10A cells
STAT3↓, thus inducing inhibition of the STAT3 signaling pathway in multiple myeloma cells
NRF2↑, Nrf2) activation has been found to mediate the upregulation of heme oxygenase-1 (HO-1) in piperlongumine treated MCF-7 and MCF-10A cells
HO-1↑,
PTEN↑, stimulates ROS accumulation; p53, p27, and PTEN overexpression
P-gp↓, P-gp, MDR1, MRP1, survivin, p-Akt, NF-κB, and Twist downregulation;
MDR1↓,
MRP1↓,
survivin↓,
Twist↓,
AP-1↓, iperlongumine significantly suppresses the expression of transcription factors, such as AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6, and YY1.
Sp1/3/4↓,
STAT1↓,
STAT6↓,
SOX4↑, increased expression of p21, SOX4, and XBP in B-ALL cells
XBP-1↑,
P21↑,
eff↑, combined use of piperlongumine with cisplatin enhances the sensitivity toward cisplatin by inhibiting Akt phosphorylation
Inflam↓, inflammation (COX-2, IL6); invasion and metastasis, such as ICAM-1, MMP-9, CXCR-4, VEGF;
COX2↓,
IL6↓,
MMP9↓,
TumMeta↓,
TumCI↓,
ICAM-1↓,
CXCR4↓,
VEGF↓,
angioG↓,
Half-Life↝, The analysis of the plasma of piperlongumine treated mice (50 mg/kg) after intraperitoneal administration, 1511.9 ng/ml, 418.2 ng/ml, and 41.9 ng/ml concentrations ofplasma piperlongumine were found at 30 minutes, 3 hours, and 24 hours, respecti
BioAv↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine

96- QC,  docx,    Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways
- vitro+vivo, Pca, LNCaP - in-vitro, Pca, PC3
PI3K/Akt↓, PI3K/Akt signaling pathway was excessively activated after prostate cancer cells developed resistance to docetaxel. And quercetin could also reverse the activation of this pathway.
Ki-67↓,
BAX↑,
Bcl-2↓,
EpCAM↓,
Twist↓, Twist2
E-cadherin↑,
P-gp↓, Quercetin reverses docetaxel resistance by reversing the up-regulation of P-gp
TumCP↓, quercetin had the reversal effect of docetaxel-resistance, which could inhibit cell proliferation, migration, invasion and colony formation of docetaxel-resistant prostate cancer cells.
TumCMig↓,
TumCI↓,

926- QC,  PacT,  doxoR,  Tam,    Bioenhancers from mother nature and their applicability in modern medicine
- Review, Nor, NA
*BioEnh↑, Piperine, obtained from the oleoresin in the peppercorns is by far the most studied and researched bioenhancer.
BioEnh↑, In a study, pretreatment of quercetin (5.0 and 15 mg/kg) half an hour before verapamil (10 mg/kg) administration significantly altered the pharmacokinetics of verapamil.
BioEnh↑, genistein (10 mg/kg) caused an increase in AUC (54.7%) and a decrease in the total plasma clearance (35.2%) after oral administration of paclitaxel
BioEnh↑, Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before and after intravenous administration of paclitaxel (3 mg/kg), the AUC was significantly improved (40.8% and 49.1% for naringin doses
BioEnh↑, One of the widely used bioenhancers is Capmul MCM C10, a glyceryl monocaprate, produced from edible fats and oils and is commonly used in lip products.
BioEnh↑, Nitrite glycoside is a bioenhancer for drugs and nutrients. Novel bioactive nitrile glycosides, niaziridin and niazirin is obtained from the leaves, pods, and bark of Moringa oleifera
BioEnh↑, Cow urine distillate is more effective as bioenhancer than cow urine, to increase the effectiveness of antimicrobial, antifungal, and anticancer drugs.
P-gp↓, Bioavailability-enhancing activity of natural compounds from the medicinal plants may be attributed to various mechanisms, such as P-gp inhibition activity by flavone, quercetin, and genistein

923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
ROS↑, decided by the availability of intracellular reduced glutathione (GSH),
GSH↓, extended exposure with high concentration of quercetin causes a substantial decline in GSH levels
Ca+2↝,
MMP↓,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
other↓, when p53 is inhibited, cancer cells become vulnerable to quercetin-induced apoptosis
*ROS↓, Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors.
*NRF2↑, Moreover, the therapeutic efficacy of QC has also been defined in rat models through the activation of Nrf-2/HO-1 against high glucose-induced damage
HO-1↑,
TumCCA↑, QC increases cell cycle arrest via regulating p21WAF1, cyclin B, and p27KIP1
Inflam↓, QC-mediated anti-inflammatory and anti-apoptotic properties play a key role in cancer prevention by modulating the TLR-2 (toll-like receptor-2) and JAK-2/STAT-3 pathways and significantly inhibit STAT-3 tyrosine phosphorylation within inflammatory ce
STAT3↓,
DR5↑, several studies showed that QC upregulated the death receptor (DR)
P450↓, it hinders the activity of cytochrome P450 (CYP) enzymes in hepatocytes
MMPs↓, QC has also been shown to suppress metastatic protein expression such as MMPs (matrix metalloproteases)
IFN-γ↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α,
IL6↓,
COX2↓,
IL8↓,
iNOS↓,
TNF-α↓,
cl‑PARP↑, Induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, mitochondrial membrane depolarization,
Apoptosis↑, increased apoptosis and p53 expression
P53↑,
Sp1/3/4↓, HT-29 colon cancer cells: decreased the expression of Sp1, Sp3, Sp4 mrna, and survivin,
survivin↓,
TRAILR↑, H460 Increased the expression of TRAILR, caspase-10, DFF45, TNFR 1, FAS, and decreased the expression of NF-κb, ikkα
Casp10↑,
DFF45↑,
TNFR 1↑,
Fas↑,
NF-kB↓,
IKKα↓,
cycD1/CCND1↓, SKOV3 Reduction in cyclin D1 level
Bcl-2↓, MCF-7, HCC1937, SK-Br3, 4T1, MDA-MB-231 Decreased Bcl-2 expression, increasedBax expression, inhibition of PI3K-Akt pathway
BAX↑,
PI3K↓,
Akt↓,
E-cadherin↓, MDA-MB-231 Induced the expression of E-cadherin and downregulated vimentin levels, modulation of β-catenin target genes such as cyclin D1 and c-Myc
Vim↓,
β-catenin/ZEB1↓,
cMyc↓,
EMT↓, MCF-7 Suppressed the epithelial–mesenchymal transition process, upregulated E-cadherin expression, downregulated vimentin and MMP-2 expression, decreased Notch1 expression
MMP2↓,
NOTCH1↓,
MMP7↓, PANC-1, PATU-8988 Decreased the secretion of MMP and MMP7, blocked the STAT3 signaling pathway
angioG↓, PC-3, HUVECs Reduced angiogenesis, increased TSP-1 protein and mrna expression
TSP-1↑,
CSCs↓, PC-3 and LNCaP cells Activated capase-3/7 and inhibit the expression of Bcl-2, surviving and XIAP in CSCs.
XIAP↓,
Snail↓, inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter
Slug↓,
LEF1↓,
P-gp↓, MCF-7 and MCF-7/dox cell lines Downregulation of P-gp expression
EGFR↓, MCF-7 and MDA-MB-231 cells Suppressed EGFR signaling and inhibited PI3K/Akt/mTOR/GSK-3β
GSK‐3β↓,
mTOR↓,
RAGE↓, IA Paca-2, BxPC3, AsPC-1, HPAC and PANC1 Silencing RAGE expression
HSP27↓, Breast cancer In vivo NOD/SCID mice Inhibited the overexpression of Hsp27
VEGF↓, QC significantly reversed an elevation in profibrotic markers (VEGF, IL-6, TGF, COL-1, and COL-3)
TGF-β↓,
COL1↓,
COL3A1↓,

3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC),which act as reducing agents by chelating transition-metal ions.
*ROS↓, Quercetin is a potent scavenger of reactive oxygen species (ROS), protecting the organism against oxidative stress
*angioG↓,
*Inflam↓, anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis;
*BioAv↓, It is known that the bioavailability of quercetin is usually relatively low (0.17–7 μg/mL), less than 10% of what is consumed, due to its poor water solubility (hydrophobicity), chemical stability, and absorption profile.
*Half-Life↑, their slow elimination since their half-life ranges from 11 to 48 h, which could favor their accumulation in plasma after repeated intakes
*GSH↑, Animal and cell studies have demonstrated that quercetin induces the synthesis of GSH
*SOD↑, increase in the expression of superoxide dismutase (SOD), catalase (CAT), and GSH with quercetin pretreatment
*Catalase↑,
*Nrf1↑, quercetin accomplishes this process involves increasing the activity of the nuclear factor erythroid 2-related factor 2 (NRF2), enhancing its binding to the ARE, reducing its degradation
*BP↓, quercetin has been shown to inhibit ACE activity, reducing blood pressure
*cardioP↑, quercetin has positive effects on cardiovascular diseases
*IL10↓, Under the influence of quercetin, the levels of interleukin 10 (IL-10), IL-1β, and TNF-α were reduced.
*TNF-α↓,
*Aβ↓, quercetin’s ability to modulate the enzyme activity in clearing amyloid-beta (Aβ) plaques, a hallmark of AD pathology.
*GSK‐3β↓, quercetin can inhibit the activity of glycogen synthase kinase 3β,
*tau↓, thus reducing tau aggregation and neurofibrillary tangles in the brain
*neuroP↑,
*Pain↓, quercetin reduces pain and inflammation associated with arthritis
*COX2↓, quercetin included the inhibition of oxidative stress, production of cytokines such as cyclooxygenase-2 (COX-2) and proteoglycan degradation, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1)
*NRF2↑,
*HO-1↑,
*IL1β↓, Mechanisms included decreased levels of TNF-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 (MCP-1)
*IL17↓,
*MCP1↓,
PKCδ↓, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity.
ERK↓, 50 µM resulted in the blockade of the extracellular signal-regulated kinases (ERK1/2) pathway
BAX↓, higher doses (75–100 µM) were used, as these doses reduced the expression of proapoptotic factors such as Bcl-2-associated X protein (Bax) and caspases 3 and 9
cMyc↓, induce apoptosis at concentrations of 80 µM and also causes a downregulation of cellular myelocytomatosis (c-myc) and Kirsten RAt sarcoma (K-ras) oncogenes
KRAS↓,
ROS↓, compound’s antioxidative effect changes entirely to a prooxidant effect at high concentrations, which induces selective cytotoxicity
selectivity↑, On the other hand, when noncancerous cells are exposed to quercetin, it exerts cytoprotective effects;
tumCV↓, decrease cell viability in human glioma cultures of the U-118 MG cell line as well as an increase in death by apoptosis and cell arrest at the G2 checkpoint of the cell cycle.
Apoptosis↑,
TumCCA↑,
eff↑, quercetin combined with doxorubicin can induce multinucleation of invasive tumor cells, downregulate P-glycoprotein (P-gp) expression, increase cell sensitivity to doxorubicin,
P-gp↓,
eff↑, resveratrol, quercetin, and catechin can effectively block the cell cycle and reduce cell proliferation in vivo
eff↑, cotreatment with epigallocatechin gallate (EGCG) inhibited catechol-O-methyltransferase (COMT) activity, decreasing COMT protein content and thereby arresting the cell cycle of PC-3 human prostate cancer cells
eff↑, synergistic treatment of tamoxifen and quercetin was also able to inhibit prostate tumor formation by regulating angiogenesis
eff↑, coadministration of 2.5 μM of EGCG, genistein, and quercetin suppressed the cell proliferation of a prostate cancer cell line (CWR22Rv1) by controlling androgen receptor and NAD (P)H: quinone oxidoreductase 1 (NQO1) expression
CycB/CCNB1↓, It can also downregulate cyclin B1 and cyclin-dependent kinase-1 (CDK-1),
CDK1↓,
CDK4↓, quercetin causes a decrease in cyclins D1/Cdk4 and E/Cdk2 and an increase in p21 in vascular smooth muscle cells
CDK2↓,
TOP2↓, quercetin is known to be a potent inhibitor of topoisomerase II (TopoII), a cell cycle-associated enzyme necessary for DNA replication
Cyt‑c↑, quercetin can induce apoptosis (cell death) through caspase-3 and caspase-9 activation, cytochrome c release, and poly ADP ribose polymerase (PARP) cleavage
cl‑PARP↑,
MMP↓, quercetin induces the loss of mitochondrial membrane potential, leading to the activation of the caspase cascade and cleavage of PARP.
HSP70/HSPA5↓, apoptotic effects of quercetin may result from the inhibition of HSP kinases, followed by the downregulation of HSP-70 and HSP-90 protein expression
HSP90↓,
MDM2↓, (MDM2), an onco-protein that promotes p53 destruction, can be inhibited by quercetin
RAS↓, quercetin can prevent Ras proteins from being expressed. In one study, quercetin was found to inhibit the expression of Harvey rat sarcoma (H-Ras), K-Ras, and neuroblastoma rat sarcoma (N-Ras) in human breast cancer cells,
eff↑, there was a substantial difference in EMT markers such as vimentin, N-cadherin, Snail, Slug, Twist, and E-cadherin protein expression in response to AuNPs-Qu-5, inhibiting the migration and invasion of MCF-7 and MDA-MB cells

3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, In oral cancer cells, quercetin could inhibit EMT via up-regulation of claudin-1 and E-cadherin and down-regulation of α-SMA, vimentin, fibronectin, and Slug [29]
α-SMA↑, OSC20 Invasion: ↓Migration, ↑Expression of epithelial markers (E-cadherin & claudin-1), ↑Expression of mesenchymal markers (fibronectin, vimentin, & α-SMA),
TumCP↓, quercetin significantly reduced cancer cell proliferation, cell viability, tumor volume, invasion, metastasis and migration
tumCV↓,
TumVol↓,
TumCI↓,
TumMeta↓,
TumCMig↓,
ROS↑, This anti-cancer agent induced oxidative stress and apoptosis in the cancer cells.
Apoptosis↑,
BioAv↓, The efficacy of quercetin (as lipophilic) is much impacted by its poor absorption rates, which define its bioavailability. The research on quercetin's bioavailability in animal models shows it may be as low as 10%
*neuroP↑, quercetin has been observed to exhibit neuroprotective effects in Alzheimer's disease through its anti-oxidants, and anti-inflammatory properties and inhibition of amyloid-β (Aβ) fibril formation
*antiOx↑,
*Inflam↓,
*Aβ↓,
*cardioP↑, Additionally, quercetin protects the heart by stopping oxidative stress, inflammation, apoptosis, and protein kinases
MMP↓, ↓MMP, ↑Cytosolic Cyt. C,
Cyt‑c↑,
MMP2↓, ↓Activation MMP-2 & MMP-9, ↓Expression levels of EMT inducers & MMPs, Downregulated Twist & Slug
MMP9↓,
EMT↓,
MMPs↓,
Twist↓,
Slug↓,
Ca+2↑, ↑Apoptosis, ↑ROS, ↑Ca2+ production, ↑Activities of caspase‑3, caspase‑8 & caspase‑9
AIF↑, ↑Mitochondrial release of Cyt. C, AIF, & Endo G
Endon↑,
P-gp↓, ↓ Protein levels of P-gp, & P-gp Expression
LDH↑, ↑LDH release
HK2↓, CAL27 cells) 80µM/24h Molecular markers: ↓Activities of HK, PK, & LDH, ↓Glycolysis, ↓Glucose uptake, ↓Lactate production, ↓Viability, ↓G3BP1, & YWHA2 protein levels
PKA↓,
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
GRP78/BiP↑, Quercetin controls the activation of intracellular Ca2+ and calpain-1, which then activates GRP78, caspase-12, and C/EBP homologous protein (CHOP) in oral cancer cells
Casp12↑,
CHOP↑,

1744- RosA,    Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity
- Review, Var, NA
chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↑, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells


Showing Research Papers: 1 to 50 of 58
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 58

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   CYP1A1↑, 1,   Fenton↑, 1,   Ferroptosis↑, 1,   GPx4↓, 2,   GSH↓, 4,   GSTP1/GSTπ↓, 1,   HO-1↓, 1,   HO-1↑, 3,   c-Iron↑, 1,   lipid-P↓, 2,   lipid-P↑, 1,   NRF2↑, 3,   Prx4↑, 1,   ROS↓, 3,   ROS↑, 20,   SIRT3↑, 1,   SOD↓, 1,   TrxR↓, 1,   TrxR1↓, 1,   xCT↓, 1,  

Metal & Cofactor Biology ⓘ

TfR1/CD71↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 1,   EGF↓, 1,   mitResp↓, 1,   MMP↓, 9,   OCR↑, 1,   e-Raf↓, 1,   c-Raf↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 1,   AMPK↑, 3,   ATG7↑, 1,   cMyc↓, 5,   cMyc↑, 1,   CREB↓, 1,   CYP3A2↓, 1,   ECAR↓, 1,   ERCC1↓, 1,   GLO-I↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   HK2↓, 2,   lactateProd↓, 1,   LDH↑, 1,   LDL↓, 1,   PI3K/Akt↓, 1,   PKM2↓, 1,   SIRT1↓, 2,   SIRT1↑, 1,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↓, 10,   p‑Akt↓, 3,   APAF1↑, 1,   Apoptosis↑, 17,   ATF2↓, 1,   BAX↓, 1,   BAX↑, 9,   Bax:Bcl2↑, 3,   Bcl-2↓, 10,   Bcl-xL↓, 4,   Casp↑, 3,   Casp10↑, 1,   Casp12↑, 1,   Casp3↑, 6,   cl‑Casp3↑, 2,   Casp7↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 7,   cl‑Casp9↑, 3,   cFLIP↓, 2,   Cyt‑c↑, 6,   DR5↑, 2,   Endon↑, 1,   FADD↑, 1,   Fas↓, 1,   Fas↑, 2,   FasL↑, 1,   Ferroptosis↑, 1,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 1,   MAPK↓, 3,   MAPK↑, 2,   Mcl-1↓, 1,   Mcl-1↑, 1,   MDM2↓, 2,   p27↑, 1,   p38↓, 1,   p38↑, 1,   survivin↓, 9,   TNFR 1↑, 1,   TRAILR↑, 1,   TRPV1↑, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,   EF-1α↓, 1,   Sp1/3/4↓, 4,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   cJun↑, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,   miR-409-3p↑, 1,   other↓, 1,   other↑, 3,   other↝, 3,   tumCV↓, 5,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   cl‑CHOP↑, 1,   eIF2α↑, 1,   ER Stress↑, 5,   GRP78/BiP↑, 4,   HSP27↓, 2,   HSP70/HSPA5↓, 1,   HSP90↓, 2,   IRE1↑, 1,   p‑PERK↑, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3II↑, 1,   TumAuto↑, 6,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   DNAdam↑, 9,   HIST1H3B?, 1,   P53↓, 1,   P53↑, 9,   PARP↑, 1,   cl‑PARP↑, 6,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 4,   CDK4↓, 7,   cycA1/CCNA1↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 8,   cycE/CCNE↓, 2,   P21?, 1,   P21↑, 8,   p‑RB1↓, 2,   TumCCA↑, 18,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   CD133↓, 3,   CD44↓, 1,   cFos↓, 2,   p‑cMET↑, 1,   CSCs↓, 7,   Diff↑, 1,   EMT↓, 8,   EpCAM↓, 1,   ERK↓, 4,   FOXM1↓, 1,   FOXO4↑, 1,   Gli1↓, 1,   GSK‐3β↓, 4,   HDAC↓, 2,   HDAC10↓, 1,   HH↓, 2,   mTOR↓, 10,   p‑mTOR↓, 2,   mTORC1↓, 2,   mTORC2↓, 1,   Nanog↓, 1,   Nestin↓, 2,   NOTCH1↓, 4,   NOTCH3↓, 2,   OCT4↓, 1,   PI3K↓, 8,   PTEN↑, 1,   RAS↓, 4,   RAS↑, 1,   Shh↓, 2,   Smo↓, 1,   SOX2↓, 1,   STAT1↓, 1,   STAT3↓, 6,   p‑STAT3↓, 1,   STAT6↓, 1,   TCF-4↓, 1,   TOP2↓, 1,   TumCG↓, 8,   Wnt↓, 4,  

Migration ⓘ

AntiAg↑, 1,   AP-1↓, 3,   Ca+2↑, 3,   Ca+2↝, 1,   CD31↓, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 2,   E-cadherin↑, 1,   Ki-67↓, 2,   KRAS↓, 1,   LEF1↓, 1,   miR-133a-3p↑, 1,   MMP2↓, 8,   MMP7↓, 2,   MMP9↓, 7,   MMPs↓, 5,   PKA↓, 1,   PKCδ↓, 1,   RAGE↓, 1,   Rho↑, 1,   ROCK1↓, 1,   ROCK1↑, 1,   Slug↓, 2,   SMAD3↑, 1,   Snail↓, 1,   SOX4↓, 1,   SOX4↑, 1,   TGF-β↓, 2,   TIMP1↑, 2,   TIMP2↑, 1,   TSP-1↑, 1,   TumCA↓, 1,   TumCI↓, 9,   TumCMig↓, 7,   TumCP↓, 8,   TumMeta↓, 9,   Twist↓, 5,   uPA↓, 1,   VCAM-1↓, 1,   Vim↓, 3,   Zeb1↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,   β-catenin/ZEB1↓, 7,   β-catenin/ZEB1↑, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 11,   ATF4↑, 1,   ATF4↝, 1,   EGFR↓, 6,   EPR↑, 2,   HIF-1↓, 1,   Hif1a↓, 3,   VEGF↓, 9,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

BBB↑, 3,   MRP↓, 1,   P-gp↓, 43,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   CXCR4↓, 3,   ICAM-1↓, 1,   IFN-γ↓, 1,   IKKα↓, 2,   p‑IKKα↓, 1,   IL12↑, 1,   IL1β↓, 2,   IL2↓, 1,   IL2↑, 1,   IL6↓, 4,   IL8↓, 1,   Imm↑, 3,   Inflam↓, 3,   NF-kB↓, 15,   p65↓, 1,   PD-1↝, 1,   PD-L1↓, 2,   PGE2↓, 2,   PSA↓, 1,   TNF-α↓, 2,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 8,   BioAv↑, 8,   BioAv⇅, 1,   BioAv↝, 2,   BioEnh↑, 10,   chemoR↓, 1,   ChemoSen↑, 22,   Dose↝, 3,   eff↓, 1,   eff↑, 25,   Half-Life↓, 1,   Half-Life↝, 3,   MDR1↓, 8,   MRP1↓, 2,   P450↓, 2,   RadioS↑, 4,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

AR↓, 1,   BloodF↑, 1,   BMPs↑, 2,   EGFR↓, 6,   FOXM1↓, 1,   IL6↓, 4,   Ki-67↓, 2,   KRAS↓, 1,   LDH↑, 1,   PD-L1↓, 2,   PSA↓, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   AntiTum↑, 4,   chemoP↑, 3,   ChemoSideEff↓, 1,   memory↑, 1,   OS↑, 2,   QoL↑, 2,   Remission↑, 1,   toxicity↓, 3,   toxicity↝, 2,   TumVol↓, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 310

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 3,   GPx↑, 1,   GSH↑, 3,   GSR↑, 1,   H2O2↑, 1,   HO-1↑, 3,   Keap1↑, 1,   lipid-P↓, 1,   MDA↓, 2,   Nrf1↑, 1,   NRF2↑, 4,   ROS↓, 10,   SIRT3↑, 1,   SOD↑, 4,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   CYP3A2↓, 1,   CYP3A4↓, 1,   NADPH↓, 1,   PPARγ↑, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   Bax:Bcl2↓, 1,   Casp3↓, 2,   cl‑Casp3↓, 1,   iNOS↓, 1,   JNK↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 2,   GSK‐3β↓, 1,  

Migration ⓘ

AntiAg↑, 1,   MMP9↓, 1,   p‑Rac1↓, 1,   Rho↓, 1,   ZO-1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EPR↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 6,   P-gp↓, 7,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IKKα↑, 1,   IL10↓, 2,   IL17↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 8,   MCP1↓, 1,   NF-kB↓, 3,   NF-kB↑, 1,   PGE2↓, 2,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   GABA↑, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 5,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

ABC↓, 1,   BioAv↓, 3,   BioAv↑, 3,   BioAv⇅, 1,   BioEnh↑, 2,   Dose↑, 1,   Dose↝, 2,   eff↓, 1,   eff↑, 7,   Half-Life↑, 1,   Half-Life↝, 1,   MRP1↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BP↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 4,   CardioT↓, 1,   cognitive↑, 2,   hepatoP↑, 1,   memory↑, 2,   neuroP↑, 8,   Pain↓, 1,   RenoP↑, 1,   toxicity⇅, 1,   toxicity↝, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 2,  
Total Targets: 85

Scientific Paper Hit Count for: P-gp, permeability-glycoprotein
8 borneol
6 Quercetin
4 Baicalein
4 Biochanin A
4 Capsaicin
3 Silymarin (Milk Thistle) silibinin
3 Honokiol
3 Rosmarinic acid
2 Astragalus
2 Disulfiram
2 Gambogic Acid
2 doxorubicin
2 Magnetic Fields
2 Naringin
1 Artemisinin
1 Berbamine
1 Genistein (soy isoflavone)
1 Kaempferol
1 Bacopa monnieri
1 Piperine
1 Chemotherapy
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Celecoxib
1 Cisplatin
1 Curcumin
1 immunotherapy
1 Copper and Cu NanoParticles
1 Zinc
1 EGCG (Epigallocatechin Gallate)
1 Fisetin
1 itraconazole
1 Atorvastatin
1 Phenethyl isothiocyanate
1 Piperlongumine
1 Docetaxel
1 Paclitaxel
1 tamoxifen
1 Rutin
1 salinomycin
1 SonoDynamic Therapy UltraSound
1 Vitamin K2
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:232  State#:%  Dir#:1
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