TOP1 Cancer Research Results

TOP1, Topoisomerase I: Click to Expand ⟱

Source:

Type:

Topoisomerase I (TOP1) is an essential nuclear enzyme involved in relieving DNA supercoiling during replication and transcription.
• Elevated TOP1 expression has been observed in several tumor types, such as colorectal, ovarian, breast, and lung cancers.
• Increased TOP1 levels may correlate with higher proliferation rates, as actively dividing tumor cells require efficient relief of DNA.

• In some cancers, high TOP1 expression has been associated with aggressive tumor behavior, higher grade, and potentially poorer clinical outcomes. This may be due in part to increased proliferation and/or a greater propensity for genomic instability.
• In other contexts, TOP1 expression might indicate sensitivity to TOP1-targeted therapies. For example, tumors with high TOP1 activity may respond better to chemotherapeutic agents (e.g., irinotecan) that target the enzyme, potentially improving outcomes when appropriate treatment is administered.

TOP1 is a critical enzyme in maintaining DNA integrity whose expression in cancers can reflect tumor proliferation and genomic instability. While high TOP1 expression is often associated with aggressive tumor behavior and poorer prognosis in several cancer types, it also has therapeutic relevance because tumors with elevated TOP1 may be more sensitive to TOP1 inhibitors.

Scientific Papers found: Click to Expand⟱

5582-

BetA,

Targeting mitochondrial apoptosis by betulinic acid in human cancers

Review,

Var,

Apoptosis↑, BA has been reported to induce apoptosis via a direct effect on mitochondria.
MMP↓, BA triggered loss of mitochondrial membrane potential
Cyt‑c↑, BA was shown to trigger cytochrome c in a permeability transition pore-dependent
ROS↑, Generation of ROS upon treatment with BA has been reported to be involved in initiating mitochondrial membrane permeabilization [15].
NF-kB↑, These findings indicate that the activation of NF-kB by BA promotes BA-induced apoptosis in a cell type- specific manner.
angioG↓, antiangiogenic activity of BA was linked to its mitochondrial damaging effects [33]
mtDam↑,
TOP1↓, BA can inhibit the catalytic activity of topoisomerase I
selectivity↑, normal cells of different origin have been reported to be much more resistant to BA than cancer cells pointing to some tumor selectivity [19,25,44,45].
ChemoSen↑, his suggests that BA can be used as a sensitizer in combination regimens to enhance the efficacy of anticancer therapy or to bypass some forms of drug resistance
TumCG↓, BA also suppressed tumor growth in several animal models of human cancer.
chemoPv↑, BA has also been reported to act as a chemopreventive agent.
RadioS↑, BA may also be used in combination protocols to enhance its antitumor activity, for example with chemo- or radiotherapy or with the death receptor ligand TRAIL. B

2722-

BetA,

Betulinic Acid for Cancer Treatment and Prevention

Review,

Var,

MMP↓, betulinic acid induced loss of mitochondrial membrane potential
Cyt‑c↑, betulinic acid was shown to trigger cytochrome c
cl‑Casp3↑, Cleavage of caspase-3 and -8 was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species.
cl‑Casp8↑,
ROS↑,
NF-kB↑, Betulinic acid was identified as a potent activator of NF-κB in a number of cancer cell lines
TOP1↓, betulinic acid was shown to inhibit the catalytic activity of topoisomerase I

2726-

BetA,

Betulinic acid induces DNA damage and apoptosis in SiHa cells

in-vitro,

Cerv,

SiHa

39.83 μg/ml

tumCV↓, BA was shown to destroy SiHa cells preferentially in a concentration dependent manner with a 50% inhibition of the cells at 39.83 μg/ml.
DNAdam↑, BA was coupled with DNA strand breaks, morphological changes, disruption of MMP, reactive oxygen species (ROS) generation and the cell arrest at G0/G1 stage of cell cycle.
MMP↓,
ROS↑,
TumCCA↑,
TOP1↓, It has been previously reported that inhibition of topoisomerases might be an additional mechanism of BA-induced cell death

2727-

BetA,

Betulinic acid in the treatment of breast cancer: Application and mechanism progress

Review,

BC,

mt-ROS↑, Its mechanisms mainly include inducing mitochondrial oxidative stress, regulating specific protein (Sp) transcription factors, inhibiting breast cancer metastasis, inhibiting glucose metabolism and NF-κB pathway.
Sp1/3/4↓, By triggering the degradation of Sp1, Sp3, and Sp4, betulinic acid reduces the transcriptional activity of these factors
TumMeta↓,
GlucoseCon↓,
NF-kB↓,
ChemoSen↑, BA can also increase the sensitivity of breast cancer cells to other chemotherapy drugs such as paclitaxel and reduce its toxic side effects.
chemoP↑,
m-Apoptosis↑, variety of mechanisms, including inducing mitochondrial apoptosis, inhibiting topoisomerase
TOP1↓, betulinic acid may inhibit the ability of topoisomerase I or II to properly cleave and re-ligate DNA strands.

2731-

BetA,

Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives

Review,

GBM,

Review,

Park,

Review,

AD,

BBB↑, Notably, its ability to cross the blood–brain barrier addresses a significant challenge in treating neurological pathologies.
*GSH↑, BA can also dramatically reduce catalepsy and stride length, while increasing the brain’s dopamine content, glutathione activity, and catalase activity in hemiparkinsonian rats
*Catalase↑,
*motorD↑,
*neuroP↑, in Alzheimer’s disease rat models, it can improve neurobehavioral impairments . BA has exhibited great neuroprotective properties.
*cognitive↑, BA improves cognitive ability and neurotransmitter levels, and protects from brain damage by lowering reactive oxygen species (ROS) levels
*ROS↓,
*antiOx↑, enhancing brain tissue’s antioxidant capacity, and preventing the release of inflammatory cytokines
*Inflam↓,
MMP↓, BA can decrease the mitochondrial outer membrane potential (MOMP)
STAT3↓, The compound can inhibit the signal transducer and activator of transcription (STAT) 3 signaling pathways, involved in differentiation, proliferation, apoptosis, metastasis formation, angiogenesis, and metabolism, and the NF-kB signaling pathway,
NF-kB↓,
Sp1/3/4↓, BA has shown an ability to control cancer growth through the modulation of Sp transcription factors, inhibit DNA topoisomerase
TOP1↓,
EMT↓, inhibit the epithelial-to-mesenchymal transition (EMT)
Hif1a↓, BA has also been associated with an antiangiogenic response under hypoxia conditions, through the STAT3/hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) signaling pathway
VEGF↓,
ChemoSen↑, BA has shown great potential as an adjuvant to therapy since its use combined with standard treatment of chemotherapy and irradiation can enhance their cytotoxic effect on cancer cells
RadioS↑,
BioAv↓, Despite having great potential as a therapeutic agent, it is hard for BA to fulfill the requirements for adequate water solubility, maintaining both significant cytotoxicity and selectivity for tumor cells.

2735-

BetA,

Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications

Review,

Var,

mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-ÎºB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-ÎºB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2738-

BetA,

Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vivo,

NA,

mice

TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

2737-

BetA,

Multiple molecular targets in breast cancer therapy by betulinic acid

Review,

Var,

TumCP↓, Betulinic acid (BA), a pipeline anticancer drug, exerts anti-proliferative effects on breast cancer cells is mainly through inhibition of cyclin and topoisomerase expression, leading to cell cycle arrest.
Cyc↓,
TOP1↓,
TumCCA↑,
angioG↓, anti-angiogenesis effect by inhibiting the expression of transcription factor nuclear factor kappa B (NF-κB), specificity protein (Sp) transcription factors, and vascular endothelial growth factor (VEGF) signaling.
NF-kB↓, Inhibition of NF-kB signaling pathway
Sp1/3/4↓,
VEGF↓,
MMPs↓, inhibiting the expression of matrix metalloproteases
ChemoSen↑, Synergistically interactions of BA with other chemotherapeutics are also described in the literature.
eff↑, BA is highly lipid soluble [74,75], and it readily passes through membranes, including plasma and mitochondrial membranes. BA acts directly on mitochondria
MMP↓, decreases mitochondrial outer membrane potential (MOMP), leading to increased outer membrane permeability, generation of reactive oxygen species (ROS),
ROS↑,
Bcl-2↓, reducing expression of anti-apoptotic proteins Bcl-2, Bcl-XL and Mcl-1
Bcl-xL↓,
Mcl-1↓,
lipid-P↑, BA inhibits the growth of breast cancer cells via lipid peroxidation resulting from the generation of ROS
RadioS↑, The cytotoxicity effect of BA on glioblastoma cells is not strong; however, some studies indicate that the combination of BA and radiotherapy could represent an advancement in treatment of glioblastoma [
eff↑, BA and thymoquinone inhibit MDR and induce cell death in MCF-7 breast cancer cells by suppressing BCRP [

2743-

BetA,

Betulinic acid and the pharmacological effects of tumor suppression

Review,

Var,

ROS↑, BA improves the level of reactive oxygen species (ROS) production and alters the mitochondrial membrane potential gradient, followed by the release of cytochrome c (Cyt c), which causes the mitochondrial-mediated apoptosis of tumor cells via a caspas
MMP↓,
Cyt‑c↑,
Apoptosis↑,
TumCCA↑, BA can inhibit cancer cell growth and proliferation via cell cycle arrest
Sp1/3/4↓, BA, can inhibit the protein expression of Sp1, Sp2 and Sp4 through the microRNA (miR)-27a-ZBTB10-Sp1 axis
STAT3↓, BA can downregulate the activation of STAT3 through the upregulation of Src homology 2 domain-containing phosphatase 1 (SHP-1)
NF-kB↓, NF-κB can be inhibited by reducing the activation of inhibitor of NF-κB (IκBα) kinase (IKKβ) and phosphorylation of IκBα with BA
EMT↓, nvasion and metastasis of malignancies is prevented via epithelial-mesenchymal transition (EMT) and inhibition of topoisomerase I
TOP1↓,
MAPK↑, BA leads to the activation, via phosphorylation, of pro-apoptotic MAPK proteins, P38 and SAP/JNK, the formation of ROS and the upregulation of caspase
p38↑,
JNK↑,
Casp↑,
Bcl-2↓, BA downregulates Bcl-2 and upregulates the Bax gene in HeLa cell lines
BAX↑,
VEGF↓, BA can decrease the expression of VEGF via Sp proteins, thus having an antiangiogenic role
LAMs↓, BA suppresses the expression of lamin B1 in pancreatic cancer cells

2744-

BetA,

Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential

Review,

Var,

Apoptosis↓, Various studies have demonstrated that BE is able to induce apoptosis in numerous cancer cell lines (
TumCCA↑, 10 uM concentration, BE arrests cell cycle of murine melanoma B164A5 cells in S phase.
Casp9↑, BE is involved in the sequential activation of caspase-9, caspases 3 and 7, and cleaving of poly(ADP-ribose) polymerase (PARP) (Potze et al. 2014).
Casp3↑,
Casp7↑,
cl‑PARP↑,
MMP↓, mitochondrial membrane potential loss (Li et al. 2010; Potze et al. 2014).
ROS↑, increased reactive oxygen species (ROS) production
TOP1↓, BA was also shown to inhibit the proliferation of topoisomerases and therefore express anti-proliferative activity
NF-kB↓, BA was demonstrated to inhibit activating of NF-kB

2747-

BetA,

Betulinic acid, a natural compound with potent anticancer effects

Review,

Var,

selectivity↑, potently effective against a wide variety of cancer cells, also those derived from therapy-resistant and refractory tumors, whereas it has been found to be relatively nontoxic for healthy cells
Cyt‑c↑, induces Bax/Bak-independent cytochrome-c release.
*toxicity↓, In general, BetA is concluded to be less toxic to cells from healthy tissues.
TOP1↓, topoisomerase I/II
NF-kB↓, transcription factor NF-kB
ROS↑, Consistently, in glioma cells BetA-induced ROS generation
RadioS↑, Treatment with BetA in combination with irradiation resulted in additive growth inhibition of melanoma cells.
ChemoSen↑, BetA cooperated with anticancer drugs, doxorubicin and etoposide, to induce apoptosis and to inhibit clonogenic survival in SHEP neuroblastoma cells

2752-

BetA,

Betulinic acid: a natural product with anticancer activity

Review,

Var,

selectivity↑, nontransformed cells of different origin, e.g., fibroblasts, melanocytes, neuronal cells and peripheral blood lymphocytes, have been reported to be much more resistant to the cytotoxic effect of BA than cancer cells
ChemoSen↑, BA was found to cooperate with various chemotherapeutic drugs, including doxorubicin, etoposide, cisplatin, taxol, and actinomycin D, to induce apoptosis and to inhibit clonogenic survival of tumor cells
RadioS↑, These reports suggest that using BetA as sensitizer in chemotherapy-, radiotherapy-, or TRAIL-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy.
MMP↓, BA directly induces loss of mitochondrial membrane potenti
cl‑Casp3↑, BA, induced cleavage of both caspases-8 and -3 in cytosolic extracts.
Cyt‑c↑, cytochrome c, released from mitochondria undergoing BA-mediated permeability transition, activated caspase-3 but not caspase-8 in a cell-free system.
ROS↑, Cleavage of caspases-3 and -8 was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species (ROS).
NF-kB↑, BA is a potent activator of NF-kB in a variety of tumor cell lines.
TOP1↓, BA blocks the catalytic activity of topoisomerase I by abrogating the inter- action of the enzyme and the DNA substrate

2767-

Bos,

The potential role of boswellic acids in cancer prevention and treatment

Review,

Var,

*Inflam↓, profound application as a traditional remedy for various ailments, especially inflammatory diseases including asthma, arthritis, cerebral edema, chronic pain syndrome, chronic bowel diseases, cancer
AntiCan↑,
*MAPK↑, 11-keto-BAs can stimulate Mitogen-activated protein kinases (MAPK) and mobilize the intracellular Ca(2+) that are important for the activation of human polymorphonuclear leucocytes (PMNL)
*Ca+2↝,
p‑ERK↓, AKBA prohibited the phosphorylation of extracellular signal-regulated kinase-1 and -2 (Erk-1/2) and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB
TumCI↓,
cycD1/CCND1↓, In the case of colon cancer, BA treatment on HCT-116 cells led to a decrease in cyclin D, cyclin E, and Cyclin-dependent kinases such as CDK2 and CDK4, along with significant reduction in phosphorylated Rb (pRb)
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p‑RB1↓,
*NF-kB↓, convey inhibition of NF-kappaB and subsequent down-regulation of TNF-alpha expression in activated human monocytes
*TNF-α↓,
NF-kB↓, PC-3 prostate cancer cells in vitro and in vivo by inhibiting constitutively activated NF-kappaB signaling by intercepting the activity of IkappaB kinase (IKK
IKKα↓,
MCP1↓, LPS-challenged ApoE-/- mice via inhibition of NF-ÎºB and down regulation of MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF
IL1α↓,
MIP2↓,
VEGF↓,
Tf↓,
COX2↓, pancreatic cancer cell lines, AKBA inhibited the constitutive expression of NF-kB and caused suppression of NF-kB regulated genes such as COX-2, MMP-9, CXCR4, and VEGF
MMP9↓,
CXCR4↓,
VEGF↓,
eff↑, AKBA and aspirin revealed that AKBA has higher potential via modulation of the Wnt/Î²-catenin pathway, and NF-kB/COX-2 pathway in adenomatous polyps
PPARα↓, AKBA is also responsible for down-regulation of PPAR-alpha and C/EBP-alpha in a dose and temporal dependent manner in mature adipocytes, ultimately leading to pparlipolysis
lipid-P?,
STAT3↓, activation of STAT-3 in human MM cells could be inhibited by AKBA
TOP1↓, (PKBA; a semisynthetic analogue of 11-keto-Î²-boswellic acid), had been reported to influence the activity of topoisomerase I & II,
TOP2↑,
5HT↓, (5-LO), responsible for catalyzing the synthesis of leukotrienes from arachidonic acid and human leucocyte elastase (HLE), and serine proteases involved in several inflammatory processes, is considered to be a potent molecular target of BA derivative
p‑PDGFR-BB↓, BA up-regulates SHP-1 with subsequent dephosphorylation of PDGFR-Î² and downregulation of PDGF-dependent signaling after PDGF stimulation, thereby exerting an anti-proliferative effect on HSCs hepatic stellate cells
PDGF↓,
AR↓, AKBA targets different receptors that include androgen receptor (AR), death receptor 5 (DR5), and vascular endothelial growth factor receptor 2 (VEGFR2), and leads to the inhibition of proliferation of prostate cancer cells
DR5↑, induced expression of DR4 and DR5.
angioG↓, via apoptosis induction and suppression of angiogenesis
DR4↑,
Casp3↑, AKBA resulted in activation of caspase-3 and caspase-8, and initiation of poly (ADP) ribose polymerase (PARP) cleavage.
Casp8↑,
cl‑PARP↑,
eff↑, AKBA was preincubated with LY294002 or wortmannin (inhibitors of PI3K), it caused a significant enhancement of apoptosis in HT-29 cells
chemoPv↑, chemopreventive response of AKBA was estimated against intestinal adenomatous polyposis through the inhibition of the Wnt/Î²-catenin and NF-ÎºB/cyclooxygenase-2 signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
ascitic↓, AKBA by the suppression of ascites,
Let-7↑, AKBA could up-regulate the expression of let-7 and miR-200
miR-200b↑,
eff↑, anti-tumorigenic effects of curcumin and AKBA on the regulation of specific cancer-related miRNAs in colorectal cancer cells, and confirmed their protective action
MMP1↓, . It can inhibit the expression of MMP-1, MMP-2, and MMP-9 mRNAs along with secretions of TNF-Î± and IL-1Î² in THP-1 cells.
MMP2↓,
eff↑, combined administration of metformin, an anti-diabetic drug, and boswellic acid nanoparticles exhibited significant synergism through the inhibition of MiaPaCa-2 pancreatic cancer cell proliferation
BioAv↓, BA as a therapeutic drug is its poor bioavailability
BioAv↑, administration of BSE-018 concomitantly with a high-fat meal led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA)
Half-Life↓, drug needs to be given orally at the interval of six hours due to its calculated half- life, which was around 6 hrs.
toxicity↓, BSE has been found to be a safe drug without any adverse side reactions, and is well tolerated on oral administration.
Dose↑, Boswellia serrata extract to the maximum amount of 4200 mg/day is not toxic and it is safe to use though it shows poor bioavailability
BioAv↑, Approaches like lecithin delivery form (PhytosomeÂ®), nanoparticle delivery systems like liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly (lactic-co-glycolic acid) nanoparticles
ChemoSen↑, Like any other natural products BA can also be effective as chemosensitizer

5858-

CAP,

Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health

Review,

Nor,

Review,

AD,

*BBB↓, crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition.
*GutMicro↑, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. often favoring the growth of beneficial taxa such as Ruminococcaceae, Lac
Obesity↓, These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects
*Inflam↓,
*AntiCan↑,
*TRPV1↑, Capsaicin is a potent agonist perceived by TRPV1, a transmembrane cation channel that functions with Ca2+.
*Ca+2↑, causes an increase in Ca2+ flux,
*antiOx↑, Capsaicin is a bioactive compound of chili peppers responsible for their spicy flavor, which also shows antioxidant, anti-obesity, analgesic, anti-inflammatory, anticarcinogenic, and cardioprotective effects
*cardioP↑,
*BioAv↓, capsaicin exhibits low systemic bioavailability due to its rapid metabolism in the liver and other tissues, resulting in a short plasma half-life of approximately 25 min in humans
*Half-Life↓,
*BioAv↝, Capsaicin’s bioavailability is determined by multiple interrelated factors, including its physicochemical properties, metabolic transformations, route of administration, and the biological context of the host, including gut microbiota composition.
*BioAv↑, For instance, polymeric micelles, liposomes, and hydroxypropyl-β-cyclodextrin complexes have demonstrated the capacity to enhance capsaicin’s oral bioavailability, prolong its plasma half-life, and improve therapeutic consistency
*neuroP↑, capsaicin exposure alters glutamate, GABA, and serotonin levels in distinct brain regions, with potential implications for neuroprotection, mood regulation, and energy metabolism.
Apoptosis↑, apoptosis is the main mechanism by which capsaicin induces cell death in cancer cells.
p38↑, capsaicin triggers a calcium flux within the cell via TRPV1, activating the p38 pathway.
ROS↑, As a result, reactive oxygen species (ROS) are produced, along with depolarization of the mitochondrial membrane potential and opening of the mitochondrial permeability transition pore.
MMP↓,
MPT↑,
Cyt‑c↑, Consequently, cytochrome c is released, the apoptosome is assembled, and caspases are activated, ultimately leading to cell death
Casp↑,
TRIB3↑, capsaicin enhances TRIB3 gene expression, which allowed an increase in the antiproliferative and proapoptotic effects of TRIB3 in cancer cells
NADH↓, Capsaicin has also been seen to downregulate and inhibit tumor-associated NADH oxidase (tNOX) and Sirtuin1 (SIRT1) in multiple cancer cell lines such as bladder cancer, which led to reduced cell growth and migration
SIRT1↓,
TumCG↓,
TumCMig↓,
TOP1↓, pointing out that capsaicin had an inhibitory effect on topoisomerases I and II, causing a reduction in metabolic activity and proliferation of a human colon cancer cell line
TOP2↓,
β-catenin/ZEB1↓, with capsaicin, the β-catenin transcription gets downregulated
*ROS↓, Capsaicin has also been proven to alleviate redox imbalance or oxidative stress, thanks to its antioxidative activity.
*Aβ↓, Alsheimer’s disease, attenuating neurodegeneration in mice by reducing amyloid-beta levels via the promotion of non-amyloidogenic processing of amyloid precursor protein

6026-

CGA,

Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression

Review,

Var,

ChemoSen↑, This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway.
AMPK↑, AMPK pathway is the main cell metabolic pathway that is activated by CGA in some studies.
EGFR↓, Moreover, CGA inhibited EGFR/PI3K/mTOR, HIF, VEGF pathways and MAPK/ERK pathway that may suppress tumor cell growth.
PI3K↓,
mTOR↓,
Hif1a↓, CGA Inhibits HIF-1α/AKT Pathway
VEGF↓,
MAPK↓,
ERK↓,
DNAdam↑, CGA induced intracellular DNA damage and topoisomerase I- and II-DNA complexes formation that plays a key role in apoptosis.
TOP1↓, Topoisomerase inhibitor, known as cancer killer drug, works by inducing topoisomerase-mediated DNA damage
TOP2↓,
Apoptosis↑,
*BioAv↝, Around 70% of CGA is absorbed in small intestine and colon. CGA is relatively stable in saliva and gastric acid.
*Half-Life↓, most circulating CGA is eliminated quickly from the circulatory system with half-time of 0.3 to 1.9 hours and Tmax of 0.6 to 1 hour.

2781-

CHr,

PBG,

Chrysin a promising anticancer agent: recent perspectives

Review,

Var,

PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

5810-

CPT,

CPT-11,

Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index

Review,

NA,

AntiCan↑, Camptothecin has been widely investigated over the past decades as an anti-cancer agent.
BioAv↓, However, its applications have been limited by poor water solubility, low stability, and substantial toxicity.
toxicity⇅,
TOP1↓, Camptothecin and its derivatives (CPTs) are potent antineoplastic agents that exert their effects by inhibiting DNA topoisomerase I, leading to apoptosis during cell proliferation.
Apoptosis↑,
TumCP↓,
other↝, Despite extensive research, only two CPTs, irinotecan and topotecan, have received health authority approval.
BioAv↑, CPT-11 (Figure 3A), was the first clinically evaluated water-soluble CPT derivative
other↝, The metabolism of CPT-11 involves its conversion to SN-38 primarily by the enzyme carboxylesterase (Figure 4), found in the liver and intestines
eff↑, CPT-11 remains one of the most important chemotherapeutic agents in oncology treatment. It has been moved to the first-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic colon cancer

5809-

CPT,

Cancer Therapies Utilizing the Camptothecins: A Review of in Vivo Literature

Review,

Var,

BioAv↓, CPT suffers from many limitions including poor stability and solubility
TOP1↓, DNA topoisomerase I (TOP I) is believed to be the single point of biological activity
BioAv↑, o improve solubility over CPT and 10-hydroxyCPT, solubilizing groups have been added to the quinoline ring yielding the approved therapeutics topotecan70 and irinotecan.63

5808-

CPT,

Repair of Topoisomerase I-Mediated DNA Damage

Review,

Var,

TOP1↓, Top1 is the selective target of camptothecins, which are effective anticancer agents.
AntiCan↑,
Dose?, Two camptothecin derivatives are used in cancer therapy: hycamtin (Topotecan®) and CPT-11 (Irinotecan; Camptosar®) [31].
CHK1↑, Chk1 activation by camptothecin
Chk2↑, Chk2 activation by camptothecin

5807-

CPT,

The mechanism of topoisomerase I poisoning by a camptothecin analog

Study,

NA,

TOP1↓, The mechanism of topoisomerase I poisoning by a camptothecin analog
AntiTum↑, originally discovered because of its antitumor activity (4) and was later demonstrated to cause the accumulation of topo I–DNA adducts in vitro and in vivo

2814-

CUR,

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management

Review,

Var,

*BioAv↓, curcumin’s practical application in medicine is hindered by its limited bioavailability. low solubility in water and rapid breakdown in the body
*Inflam↓, anti-inflammatory, antioxidant, and potential anticancer abilities
*antiOx↑,
AntiCan↑,
CK2↓, Curcumin exhibited an IC50 of 2.38 ± 0.15 μM against CK2α
GSK‐3β↓, roles of GSK3β and how they are suppressed by curcumin
EGFR↓, roles of EGFR and how it is inhibited by the curcumin analog, 3a
TOP1↓, unwinding of DNA supercoils by Topo I and Topo II and their inhibition by cyclocurcumin
TOP2↓,
NF-kB↓, The activation of NF-kB signaling and the inhibition of NF-kB’s activity are portrayed in Figure 5.
COX2↓, curcumin itself interacts with COX-2 and potentially inhibits its function
CRP↓, ole of CRP in inducing inflammation and its inhibition by curcumin are depicted in Figure 6.

2832-

FIS,

Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies

Review,

Var,

MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
Diablo↑,
Casp↑,
cl‑PARP↑,
Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
P21↑,
p27↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
Vim↓,
EMT↓,
Twist↓,
DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,

2906-

LT,

Luteolin, a flavonoid with potentials for cancer prevention and therapy

Review,

Var,

*Inflam↓, anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically
AntiCan↑,
antiOx⇅, With low Fe ion concentrations (< 50 μM), luteolin behaves as an antioxidant while high Fe concentrations (>100 μM) induce luteolin's pro-oxidative effect
Apoptosis↑, induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis.
TumCP↓,
TumMeta↓,
angioG↓,
PI3K↓, , luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP)
Akt↓,
NF-kB↓,
XIAP↓, luteolin inhibits PKC activity, which results in a decrease in the protein level of XIAP by ubiquitination and proteasomal degradation of this anti-apoptotic protein
P53↑, stimulating apoptosis pathways including those that induce the tumor suppressor p53
*ROS↓, Direct evidence showing luteolin as a ROS scavenger was obtained in cell-free systems
*GSTA1↑, Third, luteolin may exert its antioxidant effect by protecting or enhancing endogenous antioxidants such as glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*other↓, luteolin may chelate transition metal ions responsible for the generation of ROS and therefore inhibit lipooxygenase reaction, or suppress nontransition metal-dependent oxidation
ROS↑, Luteolin has been shown to induce ROS in untransformed and cancer cells
Dose↝, It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals
chemoP↑, may act as a chemopreventive agent to protect cells from various forms of oxidant stresses and thus prevent cancer development
NF-kB↓, We found that luteolin-induced oxidative stress causes suppression of the NF-κB pathway while it triggers JNK activation, which potentiates TNF-induced cytotoxicity in lung cancer cells
JNK↑,
p27↑, Table 1
P21↑,
DR5↑,
Casp↑,
Fas↑,
BAX↑,
MAPK↓,
CDK2↓,
IGF-1↓,
PDGF↓,
EGFR↓,
PKCδ↓,
TOP1↓,
TOP2↓,
Bcl-xL↓,
FASN↓,
VEGF↓,
VEGFR2↓,
MMP9↓,
Hif1a↓,
FAK↓,
MMP1↓,
Twist↓,
ERK↓,
P450↓, Recently, it was determined that luteolin potently inhibits human cytochrome P450 (CYP) 1 family enzymes such as CYP1A1, CYP1A2, and CYP1B1, thereby suppressing the mutagenic activation of carcinogens
CYP1A1↓,
CYP1A2↓,
TumCCA↑, Luteolin is able to arrest the cell cycle during the G1 phase in human gastric and prostate cancer, and in melanoma cells

Showing Research Papers: 1 to 24 of 24

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 24

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 3, GPx↑, 1, GSH↑, 1, GSR↑, 1, GSTA1↑, 1, MDA↓, 1, ROS↓, 4, SOD↑, 2,

Cell Death ⓘ

iNOS↓, 1, MAPK↑, 1, TRPV1↑, 1,

Transcription & Epigenetics ⓘ

other↓, 1,

Migration ⓘ

Ca+2↑, 1, Ca+2↝, 1,

Barriers & Transport ⓘ

BBB↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 6, NF-kB↓, 2, TNF-α↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↑, 1, BioAv↝, 2, Half-Life↓, 2,

Clinical Biomarkers ⓘ

AST↓, 1, GutMicro↑, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, cardioP↑, 1, cognitive↑, 1, hepatoP↑, 1, motorD↑, 1, neuroP↑, 3, toxicity↓, 1,
Total Targets: 34

Scientific Paper Hit Count for: TOP1, Topoisomerase I

12 Betulinic acid
4 Camptothecin
2 Chrysin
1 Boswellia (frankincense)
1 Capsaicin
1 Chlorogenic acid
1 Propolis -bee glue
1 irinotecan
1 Curcumin
1 Fisetin
1 Luteolin

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#:1117  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

TOP1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Migration ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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