toxicity Cancer Research Results
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TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA
toxicity↑, 3-Bromopyruvate (3BP), a small alkylating
agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity
across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis
through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK-
cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on
liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol
formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and
C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.
toxicity↑, German police took action on 4 August after two patients from the Netherlands and one from Belgium died shortly after undergoing treatment at the Biological Cancer Centre, run by alternative practitioner Klaus Ross in the town of Brüggen, Germany
Glycolysis↓, It is believed to "starve" tumor cells to death by inhibiting glycolysis, the breakdown of glucose molecules to provide cells with energy.
eff↑, experiments on human cancer cell lines showed that combining another chemotherapeutic with 3BP increased its efficacy.
OS↑, the patient "was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP,
QoL↑,
toxicity↝, Vogl says doctors should "absolutely" not perform systemic infusions, in which the drug circulates through the entire body. "
*toxicity↑, A 44-year-old previously well man ingested ten times the recommended dose of 5-HTP powder. After four hours he developed marked antegrade and retrograde amnesia, disorientation and confusion in the absence of loss of consciousness, seizure activity o
*Dose↑, A previously well 44-year-old male was admitted following inadvertent intake of 800 mg of powdered 5-HTP supplement, instead of the intended 80 mg
*toxicity↑, We show that peak X is actually a family of contaminants with the same molecular weight (234 Da) and similar HPLC retention times. We also demonstrate that all eight samples of commercially available 5-OHTrp analyzed by HPLC-MS contained three or mor
*Dose↝, Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study
*other↑, The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity.
*LDL↓, significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels.
*HDL↑,
*toxicity↑, No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo.
*ROS↓, In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.
TumCD↑, curcumin has been shown to modulate immunoediting processes including resurrecting immune surveillance mechanisms to help eradicate cancer cells
TumCG↓, studies by Lee-Chang et al34 have shown that administration of resveratrol, a dietary polyphenol compound possessing antioxidant properties at low doses that are nontoxic to immune cells, inhibits lung metastasis of breast cancer tumor.
ROS⇅, Of importance, resveratrol can exert both antioxidant and pro-oxidant properties depending on its concentration and cell types used
eff↑, Wang et al36 have demonstrated that a combination of fish oil and selenium that possesses anti-inflammatory and antioxidant activities exerted synergistic effects in suppressing lung tumor growth mediated via decreasing the population of splenic Treg
RadioS↑, Several nutritional cancer chemopreventive compounds having antioxidant properties have been documented to potentiate radiation therapy–induced cytotoxic effects on cancer cells while reducing its toxicity on normal surrounding tissues.77-86
TumCG↓, soy isoflavone component genistein on prostate cancer demonstrated that both soy and genistein inhibited the growth of in vitro human PC-3 prostate cancer cells and in vivo orthotopic PC-3 tumors
OS↑, While a statistically significant improved survival rate either at 1 year or 5 years was associated with melatonin supplementation
toxicity∅, 9 RCTs reported no differences in the toxicities by antioxidants supplementation
toxicity↑, and 1 RCT with vitamin A reported increased toxicity.
AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2/PTGS2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value
Imm↑, β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models.
*Dose↝, Subjects were randomized to either the β -glucan (n = 10) or the control group (n = 5). Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days.
*BioAv↓, β-glucan was barely detectable in serum of volunteers at all time-points.
*toxicity↑, Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.
*glucoNG↓, These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis
*Glycolysis↑,
*NH3↑, inhibited ammonia detoxification
*NADPH/NADP+↑,
*ATP↓,
*toxicity↑, narrow margin between the expected benefits and toxicity
TumCP↓, mechanism of action of celastrol in terms of inhibition of cell proliferation and regulation of the cell cycle, regulation of apoptosis and autophagy, inhibition of cell invasion and metastasis, anti-inflammation, regulation of immunotherapy, and an
TumCCA↑,
Apoptosis↑,
TumAuto↑,
TumCI↓,
TumMeta↓,
Imm↝,
angioG↓,
Cyt‑c↑, release of cytochrome c (CytC)
ROS↑, increasing ROS levels, and activating the mitochondrial apoptosis pathway
BAX↑, upregulating the expression of CytC and the pro-apoptotic protein Bax, activating caspase-3 and caspase-9, and leading to the cleavage of PARP
Casp3↑,
Casp9↑,
cl‑PARP↑,
PrxII↓, binds to peroxiredoxin-2 (Prdx2) and inhibits its enzyme activity,
ER Stress↑, resulting in ROS-dependent endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells
mtDam↑,
CHOP/DDIT3↑, celastrol upregulates the expression of CHOP, Bip, XBP1s, and IRE1 proteins,
Inflam↓, Anti-inflammatory properties of celastrol
NF-kB↓, Celastrol additionally obstructed NF-κB and its downstream gene products, such as CXCR4 and MMP9, and reduced serum IL-6 and TNF-α levels to inhibit cell invasion and migration in vivo
CXCR4↓,
MMP9↓,
IL6↓,
TNF-α↓,
HSP90↓, accumulation may be due to the inhibition of HSP90 and the stress response
neuroP↑, Our mass spectrometry research also showed that celastrol directly binds to HSP90 and HSP70, exerting antitumor and neuroprotective effects
STAT3↓, Celastrol exerts anti-tumor activity by inhibiting STAT3
Prx↓, celastrol binds directly to Prdx1, Prdx2, Prdx4, and Prdx6 via active cysteine sites, inhibiting their antioxidant activity without affecting protein expression
HO-1↑, Celastrol also targeted heme oxygenase-1 (HO-1), increasing its expression in activated hematopoietic stem cells
eff↑, Research has indicated that celastrol, combined with 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), inhibits the toxic stress response of HSP90-targeted proteins, reduces the sensitization of human glioblastomas to celastrol treatment, an
eff↑, celastrol, when combined with EGFR tyrosine kinase inhibitors (EGFR-TKIs), effectively inhibits the growth and invasion of T790M mutant human lung cancer H1975
BioAv↑, nano-delivery systems present a novel pathway for the development and clinical application of celastrol, potentially overcoming existing limitations and maximizing its therapeutic potential.
toxicity↑, several significant challenges, including its pronounced hepatic and renal toxicity and potential for causing immunosuppression
CardioT↑, celastrol, which includes hepatotoxicity, cardiotoxicity, infertility toxicity, hematopoietic system toxicity and nephrotoxicity.
hepatoP↓,
*ROS↑, The literature evidences that the CuO NPs exposure to the living systems results in reactive oxygen species generation, oxidative stress, inflammation, cytotoxicity, genotoxicity and immunotoxicity.
*Inflam↑,
*toxicity↑,
lipid-P↑, A549 cells that leads to high level of lipid peroxidation and ROS production while lower level of antioxidant (GSH) in HepG2
GSH↓,
MDA↑, They observed that MDA, a lipid peroxidation marker and antioxidant enzymes like SOD and CAT significantly increased followed by reduction in GSH level
*SOD↓, Lower level of GSH and inhibition of SOD and CAT activities by CuO NPs contributing to oxidative damages was also observed in embryo and while change in zebrafish physiology
*Catalase↓,
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*toxicity↑, The emergence of natural products has provided extremely valuable references for the treatment of various diseases. Cucurbitacin B, a tetracyclic triterpenoid compound isolated from cucurbitaceae and other plants, is the most abundant member of the c
*antiOx↑, cucurbitacin B and cucurbitacin I have antioxidant properties, which can inhibit lipid peroxides
*Inflam↓, These results suggest that cucurbitacin B can inhibit the activation of NLRP3 inflammasome to inhibit the inflammatory response and cell damage in brain I/R injury.
*NLRP3↓,
*NF-kB↓, cucurbitacins B, E, and I can significantly reduce the activation activity of NF-κB induced by TLR 2/4 agonists in cells.
*neuroP↑, administration of cucurbitacin B has been shown to enhance the generation of new neurons in the hippocampus of ICR and APP/PS1 mice, thereby ameliorating the working memory deficits observed in these mice models
*memory↑,
*GABA↑, Concurrently, cucurbitacin B enhanced the levels of GABA.
*cardioP↑, cucurbitacin B exerts protective effects on the heart, including the prevention of hypertrophy, the amelioration of compromised cardiac function following myocardial infarction,
AntiTum↑, Cucurbitacin B has cytotoxic activity on a variety of tumor cells (Figure 5), and it has a good clinical application prospect as an antitumor drug.
p‑FAK↓, cucurbitacin B inhibited the phosphorylation of FAK and paxillin, and it could also induce the production of reactive oxygen species (ROS), which is helpful for the anti-metastatic potential of the cells.
ROS↑,
TumMeta↑,
TumCP↓, cucurbitacin B induced early apoptosis in these cells and altered the expression of proteins involved in proliferation and apoptosis, such as up-regulating the p53 and p21 genes.
Apoptosis↑,
P53↑,
P21↑,
TumCCA↑, cucurbitacin B affected the cell cycle transition from the G0/G1 phase to the S phase.
p27/CDKN1B↑, cucurbitacin B upregulated the expression of p27 and downregulated the expression of CDK4, CDK2, cyclin D1, and cyclin E mRNA.
CDK4↓,
CDK2↓,
cycD1/CCND1↓,
cycE/CCNE↓,
STAT3↓, inhibiting the STAT3 signaling pathway
ChemoSen↑, combination of cucurbitacin B and cisplatin (DDP) enhanced the activation of caspase-3 and the cleavage of caspase-3 substrate PARP, and it decreased the expression level of pSTAT3.
MMP2↓, It may down-regulate the expression of MMP2, MMP9, and VEGF, which could significantly inhibit cell migration and angiogenesis.
MMP9↓,
VEGF↓,
TumCMig↓,
angioG↓,
NOTCH↓, the Notch signaling pathway in LNCaP cells was down-regulated.
EMT↓, Additionally, it inhibits the epithelial–mesenchymal transition (EMT) mediated by TGF-β1
toxicity↑, Cucurbitacin B exhibits good activity against HepG2 cells, but its high toxicity results in a low therapeutic index (TI).
BioAv↑, Cu-B SLNs can passively target tumors with the EPR effect and show higher accumulation in tumor interstitial space, which can improve the efficacy of cucurbitacin B and reduce the dose.
EPR↑,
PDK1↓, Specifically, it inhibits pyruvate dehydrogenase kinase, which may convert metabolism from fermentative glycolysis back to oxidative phosphorylation.
Apoptosis↑, This process may induce cancer cell apoptosis through several mechanisms including increased oxidative stress and reduced lactate levels.
ROS↑,
lactateProd↓,
Dose↝, DCA can be administered orally or intravenously.
eff↝, overall, there is insufficient evidence to support the efficacy of DCA as a cancer treatment.
toxicity↓, most studies have found DCA to be reasonably safe and well tolerated, The most common side effect is reversible peripheral neuropathy.
NP/CIPN↑, One of the five patients who entered the trial with some degree of peripheral neuropathy developed a score of 3 in the Total Neuropathy Score (TNS), but this resolved within six months after DCA cessation
Dose↝, doses range from 10-50mg/kg daily, with the most common oral dosing being 6.25-12.5mg/kg taken twice daily.
*BioAv↑, DCA is a small water soluble molecule of 150 Da, allowing it to achieve 100% bioavailability when given either orally or intravenously
*Half-Life↓, Serum DCA levels rise rapidly after oral administration and exhibit a relatively short half-life. elimination half-life of 92 minutes
GSTZ1↝, DCA metabolism is affected by glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI)
genotype status. Individuals with at least one wild-type haplotype metabolize DCA more rapidly and thus may be able to tolerate a higher dose
Glycolysis↓, DCA acts on the mitochondrial matrix of cancer cells, diverting metabolism from fermentative glycolysis back
to oxidative phosphorylation
OXPHOS↑,
MPT↑, reopening of voltage and redox sensitive mitochondrial transition pores (22). This allows for the pro-apoptotic mediators, cytochrome c and apoptosis-inducing-factor, to be released into the cytoplasm,
Cyt‑c↑,
AIF↑,
Casp↑, increasing the levels of pro-apoptotic ROS through the activation of caspases
CSCs↓, Although less well established, there is some evidence that DCA may be able to reduce stemness and induce differentiation in cancer stem cells
Remission↑, rigorous treatment cycle with DCA, alpha lipoic acid, and B vitamins and achieved complete remission of his
cancer as evidenced by PET scans, CT scans, and laboratory testing. Four years later, the patient remained
cancer free.
ChemoSen↑, Several preclinical studies have demonstratedsynergistic effects of DCA with chemotherapeutic agents, including carboplatin (34, 57), oxaliplatin (34, 57), 5-fluorouracil (29), paclitaxel (58, 59), doxorubicin (60), elesclomol (24), and sorafenib (6
RadioS↑, There is preliminary preclinical evidence that DCA may act as a radiosensitizer primarily by increasing levels of reactive oxygen species in tumour cells
toxicity↑, Combined with artesunate one patient experienced fatal liver and bone marrow toxicity.
TumCP↓, Deguelin demonstrates anticancer activity by suppressing cell proliferation and promoting apoptosis via the modulation of critical signaling pathways, such as NF-κB, Wnt, and AMPK pathways.
Apoptosis↑,
NF-kB↓, Several studies have shown that deguelin treatment can inhibit NF-κB activation, thereby inducing apoptosis in multiple cell types.
Wnt↓,
TumCCA↑, including cell cycle arrest, autophagy modulation, anti-angiogenic and anti-metastatic capabilities, along with antioxidant and anti-inflammatory actions.
TumMeta↑,
antiOx↑,
Inflam↓,
angioG↓, deguelin can inhibit angiogenesis and tumor metastasis through a variety of targets, such as MMPs, HIF-1α, FAK and PI3K/Akt pathway
Half-Life↑, . It exhibited a long mean residence time (6.98 h) and a terminal half-life of 9.26 h, supporting its potential for once-daily dosing.
MMP2↓, deguelin reduced the expression of MMP-2 and MMP-9
MMP9↓,
Casp9↑, deguelin can also induce apoptosis of gastric cancer cells through the activation of two key apoptotic pathways, caspase-9 and caspase-3
Casp3↑,
EMT↓, (NSCLC) mouse model, deguelin was found to inhibit the EMT process by promoting the expression of PTEN and KLF4,
PTEN↑,
ChemoSen↑, Its combination with conventional chemotherapy has also been shown to enhance the efficacy
toxicity↑, Long-term or high-dose deguelin administration induces a Parkinson’s disease-like condition in rats
*BBB↑, findings indicate that both deguelin and L80 can effectively penetrate the blood-brain barrier (BBB).
PI3K/Akt↓, Deguelin is a well-known PI3K/Akt inhibitor
IKKα↓,
AMP↓,
mTOR↓,
survivin↓,
NF-kB↓,
Apoptosis↑,
TumCCA↑, G1-S phase cell cycle arrest
toxicity↓, No sign of overt toxicity has been observed at the dose of 2–4 mg/kg
HSP90↓,
Casp↑, caspase cascade of apoptosis is initiated
TumCG↓,
p27/CDKN1B↑, found to regulate cell cycle in colon cancer cells by stimulating p27
cycE/CCNE↓,
angioG↓,
Hif1a↓,
VEGF↓,
*toxicity↑, Treatment with deguelin, a potential mitochondria complex I inhibitor (34), reduced tyrosine hydroxylase-positive neurons, leading to Parkinson’s disease (PD).
OS∅, clinical trial of 88 patients with recurrent glioblastoma, the addition of disulfiram and copper to alkylating chemotherapy did not significantly improve survival at 6 months,
toxicity↑, Six patients (15%) in the experimental group developed elevated liver enzymes compared with no patient in the SOC group
*toxicity↑, however, it is known that emodin, which shows toxicity to cancer cells, may cause kidney toxicity, hepatotoxicity, and reproductive toxicity especially at high doses and long-term use.
*BioAv↓, poor oral bioavailability
Akt↓,
ERK↓,
ROS↑, pretreatment of cells with ascorbic acid prevented the induction of ROS by emodin and inhibited the upregulation of p53
MMP↓,
Bcl-2↓,
BAX↑,
TumCCA↑, increasing the percentage of both S and G2/M phase cells
AntiCan↑, Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural compound derived from traditional Chinese and Japanese medicine, has recently garnered significant attention for its potential anticancer properties.
*antiOx↑, Emodin exerts its chemoprotective effects through a combination of antioxidative, anti-inflammatory, and anti-proliferative mechanisms.
*chemoP↑,
*Inflam↓,
TumCP↓,
TumMeta↓, emodin inhibits cancer metastasis, disrupts cell cycle progression, and impairs cancer cell survival.
TumCCA↑,
MAPK↑, activation of the p38 MAPK/JNK1/2 signaling pathway, the upregulation of pro-apoptotic factors such as Bax/Bcl-2 and caspases, and the enhancement of reactive oxygen species (ROS) levels (
BAX↑,
Casp↑,
ROS↑,
*BioAv↓, The pharmacokinetic limited properties of emodin significantly affect its bioavailability and bioactivity, hence limiting its therapeutic uses.
other↝, Chinese medicinal herbs contains emodin, which is utilized in traditional Chinese and Japanese medicine, include Rheum palmatum, Polygonum cuspidatum, and Cassia obtusifolia
TumCI↓, including as invasion and metastasis, tumour angiogenesis, epithelial-mesenchymal transition (EMT), cell growth (i.e., promotion of apoptosis, reduction of proliferation, and changed cellular redox status).
EMT↓,
TumCG↑,
Apoptosis↑,
TumCP↑,
MMP2↓, inhibit cell invasion by modulating and down regulating the activation and expression of MMP2, Bax/Bcl-2 and caspase-3 involving in esophageal cancer
Casp3↑,
ChemoSen↑, When combined with ciplatin, emodin significantly raises intracellular ROS, which improves proapoptotic effects and can be used to treat esophageal cancer
PI3K↓, figure 3
Akt↓,
Cyt‑c↑,
cl‑PARP↑,
MMP↓, emodin trigger the mitochondria of GI cancer cells to disrupt mitochondrial membrane potential by signaling molecules Bax, Bak PARP and triggers the release of cytochrome c to activate caspase -9 and 3 culminating into apoptosis
Warburg↓, Hepatic carcinoma HepG2 cells 20–200 µM Reduces wadburg effect by ↓ HKII, PKM2, LDHA, limiting energy supply, ↑ ROS production, ↑ mitochondrial damage and apoptosis
HK2↓,
PKM2↓,
LDHA↓,
mtDam↑,
Apoptosis↑,
N-cadherin↓, Ovarian cancer SK-OV-3, A2780, PA-1 2.5–80 µM Inhibited EMT by ↓ N cadherin & vimentin and ↑ E-cadherin
Vim↓,
E-cadherin↑,
eff↑, EMO exhibits broader range of pharmacological activities and in combination with nano range molecules.
eff↑, chitosan oligosaccharide nano-micelles (CSO-SA-EMO) significantly enhanced antioncogenic properties against the gastric cancer cells.
eff↑, Fe3O4- PEG-Cy7-EMO nanoparticles also proved potential nanoplatform in pancreatic tumor xenografted mice.
toxicity↝, emodin treatment at a maximum dose of 80 mg/Kg body weight orally and 40 mg/Kg body weight intraperitoneally does not significantly harm patients.
toxicity↑, emodin dosage higher than 500–1500 mg/Kg of body weight may cause toxicity such as hepatotoxicity and inflammation
*toxicity↑, presence of estragole in Malaysian natural products may raise health concern, especially when it is consumed daily over extended period.
*Dose↝, In the present study, nine (9) out of thirty (30) PFS samples obtained from Malaysian market were found
to contain estragole at various levels, from 55.0 to 418.0 μg/g.
AntiTum↑, In recent years, the antitumor, cardioprotective, anti-inflammatory, and anti-Alzheimer’s disease effects of EVO have been reported.
cardioP↑,
Inflam↓,
TumCP↓, EVO exerts antitumor effects by inhibiting tumor cell activity and proliferation, blocking the cell cycle, promoting apoptosis and autophagy, and inhibiting the formation of the tumor microvasculature.
TumCCA↑,
Apoptosis↑,
TumAuto↑,
BioAv↓, However, EVO has poor solubility and low bioavailability.
toxicity↑, Current research found that EVO could have toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiac toxicity.
NF-kB↓, SMMC-7721 and HepG2 Cells Inhibiting NOD1 to suppress NF-κB and MAPK activation
MAPK↓,
NOD1↓,
p‑Akt↓, HepG2, SMMC-7721 and H22 cell; H22 xenograft mouse model Decreased p-Akt levels activated by SC79, which led to the increase of bax/bcl-2 and cleaved-caspase3.
BAX↑,
cl‑Casp3↑,
γH2AX↑, TPC-1 and SW1736 human thyroid carcinoma cells Increased the protein levels of γH2AX and cleaved PARP, and ROS production
cl‑PARP↑,
ROS↑,
BBB↑, EVO can passively diffuse through the single-cell blood-brain barrier.
neuroP↑, It showed a concentration-dependent neuroprotective effect on PC12 cells injured by MPP+ or H2O2, indicating its potential as a neuroprotective drug
BioAv↑, nanoparticles had a size of 183.23 nm and showed better absorption than free EVO in the entire gastrointestinal tract. The relative bioavailability was 4.58 times that of free EVO.
toxicity↑, Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subs
*Dose↝, Doses of 400–500 mcg are recommended and included in prenatal multivitamins by the Department of Health in Australia [57], whereas the United States, the Centers for Disease Control and Prevention recommends 800 mcg per day
*Dose↝, in Canada at least 1000 mcg of FA are typically found in a prenatal multivitamin
*toxicity↑, After discontinuation of the self-administration of fenbendazole, the patient's liver dysfunction spontaneously resolved.
Dose↑, 1 g orally per day for 3 consecutive days, followed by 4 days off. She repeated this weekly schedule for approximately one month, from early July until August 9, 2019
*toxicity↑, confirmed severe drug-induced liver injury, hepatocellular pattern, associated with the self-administration of fenbendazole in a 67-year-old woman who presented with 2 weeks of jaundice.
Dose↑, Fenbendazole 3 g per dose, three times per week—specifically, three 1-g packets each dosing day.
toxicity↑, 47-year-old woman with metastatic colon cancer on nivolumab/relatlimab who developed severe hepatocellular liver injury after increasing her self-administered dose of fenbendazole.
Dose↑, initial dose: 222 mg, three times per week for six weeks Weekly exposure: 666 mg/week
Escalated dose: 222 mg every day Weekly exposure: 1,554 mg/week
toxicity↑, jaundice, and abdominal pain following a 3-month regimen of alternating these agents daily at a dosage of “one squirt”
Dose↑, (estimated to be 0.18 mg/kg of ivermectin and 0.98 mg/kg of fenbendazole)
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*antiOx↑, Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS
*ROS↓, The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders.
*neuroP↑,
*NO↑, inhibits NO production.
BioAv↝, oral bioavailability of fisetin was reported 7.8 and 31.7% for oral doses of 100 and 200 mg/kg, respectively
*BBB↑, BBB permeability, fisetin can also affect hippocampal synaptic plasticity indirectly through the peripheral system
*toxicity↑, Furthermore, it did not show signs of toxicity at doses up to 2 g/kg in an acute toxicity study with no toxicity in the histopathological analysis of the heart, lungs, kidneys, liver, stomach, intestines, spleen and reproductive organs
*eff↑, potential benefits against neurological health complications and neurodegenerative diseases like AD, PD. HD, ALS, vascular dementia, schizophrenia, stroke, depression, diabetic neuropathy and traumatic brain injury
*GSH↑, direct antioxidant activity in addition to increasing intracellular antioxidants such as glutathione
*SOD↑, fig 2
*Aβ↓,
*12LOX↓,
*COX2/PTGS2↓,
*Catalase↑, Fisetin treatment prevented behavioral deficits, increased brain antioxidant, superoxide dismutase, catalase, reduced glutathione, and BDNF
*Inflam↓, decreased serum homocysteine, and pro-inflammatory biomarkers (TNF-α, IL-6), lipid peroxidation
*TNF-α↓,
*IL6↑,
*lipid-P↓,
NF-kB↓, suppressed the up-regulation of NF-κB, and IDO-1 genes expression, and decreased the rise of IL-1β levels.
IL1β↓,
NRF2↑, fisetin treatment also restored the downregulation of Nrf-2, HO-1, and ChAT genes expression and BDNF levels in the hippocampus, suggesting its protective effect against oxidative stress
HO-1↑,
GSTs↑, Fisetin also restored the AlCl3-induced reduction in the levels of SOD, CAT, GST, and GSH in a study that analysed the effect of this compound on AlCl3-induced reactive gliosis and neuronal inflammation in the brain of mice
cognitive↑, Fisetin improves neurodegenerative disease-associated dementia, cognitive functions and behavioral abnormalities along with increasing age
*BDNF↑, Fisetin also increases BDNF activity to prevent neurodegeneration
*tau↓, fulvic acid, the main active principle, blocks tau self-aggregation, opening an avenue toward the study of Alzheimer's therapy.
*AntiAge↑, Shilajit has been known and used for centuries by the Ayurvedic medicine, as a rejuvenator and as antiaging compound
*Strength↑, two important characteristics of a rasayana compound in the ancient Indian Ayurvedic medicine: that is, to increase physical strength and to promote human health
*Dose↝, health benefits of shilajit have been shown to differ from region to region, depending on the place from which it was extracted [3, 4].
*BioAv↑, Fulvic acid is soluble in water under different pH conditions, and because of its low molecular weight (around 2 kDa), it is well absorbed in the intestinal tract and eliminated within hours from the body
*antiOx↑, fulvic acid is known by its strong antioxidant actions [9] and likely has systemic effects as complement activator
*memory↑, figure 1 memory enhancer
*Inflam↓, fulvic acid, is known by its properties such as antioxidant, anti-inflammatory, and memory enhancer
*cognitive↑, Our laboratory has found evidence on the high activity of the Andean form of shilajit in improving cognitive disorders and as a stimulant of cognitive activity in humans
*neuroP↑, neuroprotective agent against cognitive disorders
*toxicity↝, Studies indicate the shilajit consumption without preliminary purification may lead to risks of intoxication given the presence of mycotoxin, heavy metal ions, polymeric quinones (oxidant agents), and free radicals, among others
*toxicity↑, recent studies indicate that several ayurvedic products including shilajit and other Indian manufactured products commercialized by the Internet may contain detectable heavy metals levels as lead, mercury, and arsenic
toxicity↑, The results from the studies demonstrated that rats treated with high dose (120 mg/kg) of GA for a long time can lead to the damage on the kidney and liver.
AntiTum↑, As inhibitors of SUMOylation, GAs demonstrate significant antitumor activity, and can exert antineoplastic effects through multiple pathways, which positions them as potentially promising therapeutic agents for cancer treatment.
SUMO↓,
antiNeop↑,
*Inflam↓, GAs exhibit notable anti-inflammatory, antibacterial, and antiviral properties, highlighting their multifaceted medicinal potential.
*Bacteria↓,
*AntiViral↑,
*toxicity↑, the associated risks of liver and kidney damage must not be overlooked. GAs can induce significant hepatic damage by promoting cellular apoptosis, oxidative stress, and the disruption of various metabolic processes.
*ROS↑,
*toxicity↝, Due to their recognized toxicity, the concentration of GAs is typically regulated to within 5ppm in the standardized G. biloba leaf extract EGb 761.
toxicity↑, Overall, the percentages in the extracts showed variations of 24%−36% for flavonol glycosides and 4%—11% for terpene lactones, with a wide range from < 500 (below the limit of quantification) to 90,000 ppm for ginkgolic acids
other↝, The extracts of three herbal pharmaceuticals and four dietary supplements were found to contain less than 5 ppm of ginkgolic acids, whereas its concentration in the other four dietary supplements was much greater, ranging from 392 to 8053 ppm
*toxicity↑, These results suggest that hepatotoxicity exhibited by the Hsp90 inhibitors belonging to benzoquinone ansamycins could be attributed to superoxide.
*AntiBio↑, Geldanamycin (GM), a benzoquinone ansamycin antibiotic, is a natural product inhibitor of Hsp90 with potent and broad anti-cancer properties.
HSP90↓,
AntiCan↑,
HSP90↓, Geldanamycin is a potent heat shock protein inhibitor with remarkable antiproliferative activity.
*toxicity↑, However, it shows pronounced hepatotoxicity in animal models and unfavorable pharmacokinetic properties.
*toxicity↓, review discusses the mechanism of action of geldanamycin, its pharmacokinetic properties, and the various approaches employed to alleviate its toxicity and maximize its clinical efficacy.
*BioAv↑, The derivative 17-AAG retained the potent anticancer activity of geldanamycin but with reduced hepatotoxicity and improved bioavailability.its clinical development was halted due to its low water solubility and its hepatotoxicity.
eff↑, By contrast, 17-DMAG offers several advantages over 17-AAG, such as higher water solubility, better bioavailability, reduced metabolism, and greater anticancer activity.(stopped due to its higher toxicity compared to 17-AAG )
*toxicity↓, In contrast to geldanamycin and its 17-AGG and 17-DAMG analogs, gamitrinib showed no toxicity to normal cells or tissues and did not disrupt Hsp90 homeostasis
other↝, Overall, this review highlights the therapeutic potential of geldanamycin derivatives as anticancer drugs.
HSP90↓, Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature.
*Bacteria↓, Geldanamycin (GA), a yellow colored compound first isolated from Streptomyces hygroscopicus var. geldanus in 1970 was found to possess antibacterial properties.
*toxicity↑, although GA itself has not progressed to the clinic due to unacceptable liver toxicity,
*cardioP↑, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties.
*Inflam↓, Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokin
*NF-kB↓,
*PGE2↓,
*iNOS↓,
*ROS↓, and reactive oxygen species (ROS)
*COX2/PTGS2↓, The result showed that treatment of genistein (100 µM) effectively inhibited LPS-induced upregulation of COX-2 protein leve
*toxicity↑, The findings showed that high dose oral genistein therapy appeared to be safe in MPS patients based on preliminary findings, but more testing in a larger randomised placebo controlled trial is needed to confirm safety and efficacy
*Dose↓, The estimated average dietary intake of Ge in humans is 1.5 mg/d. Ge is widely distributed in edible foods, all of which, with few exceptions, contain less than 5 ppm Ge, since higher levels are toxic to most plants
*Dose↑, germanium sesquioxide (Ge-132) and lactate-citrate-germanate (Ge lactate citrate) have been sold as "nutritional supplements" in some countries for their purported immunomodulatory effects or as health-producing elixirs, resulting in intakes of Ge si
*toxicity↑, Since 1982, there have been 18 reported cases of acute renal dysfunction or failure, including two deaths, linked to oral intake of Ge elixirs containing germanium dioxide (GeO2) or Ge-132.
*creat↑, Serum creatinine levels have been well above 400 mumol/L in such patients
*Dose↑, In 17 of 18 cases, accumulated elemental Ge intakes reportedly ranged between 16 to 328 g over a 4-36 mo period, or between 100 to 2000 times the average estimated dietary intake for human.
*other?, It is recommended that patients exposed to long-term (greater than 3 mo) Ge supplementation at levels well above the estimated daily intake be medically supervised and monitored for potential renal-, pulmonary- or neurotoxicity.
*toxicity↓, For humans, germanium is not essential and in general the toxicity of the mentioned organo-germanium compounds is low
*toxicity↑, Acute and chronic toxic effects of inorganic germanium dioxide have been demonstrated.
toxicity↑, Chronic renal failure developed in 5 patients who were taking germanium dioxide (GeO2)-containing compounds.
toxicity↑, Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2)-containing compounds have been reported in Japan.
*creat↑, Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance.
*BUN↑,
*other↑, Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group
toxicity↑, total dose of 47 g as Ge element. She was found to have renal failure (blood urea nitrogen, 44 mg/dl; serum creatinine, 2.6 mg/dl) without abnormal findings in urinalysis, and muscular and nervous damage.
AntiCan↑, This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity
toxicity↓, Due to its safety and efficacy, GBLs have become one of the most widely used herbs in Europe and the United States, with annual sales of related products reaching billions of dollars
ChemoSen↑, ginkgetin synergizes with chemotherapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects.
chemoP↑, In addition to standalone use, ginkgetin has synergistic effects with other drugs by enhancing drug efficacy and alleviating side effects.
TumCCA↑, mechanisms, including inducing cell cycle arrest, triggering programmed cell death, and preventing invasion and angiogenesis.
TumCD↑,
TumCI↓,
angioG↓,
Ferroptosis↑, figure 1
Imm↑, emerging evidence suggests that ginkgetin could enhance the body’s immunity and has an anti-tumor function
MOMP↑, ginkgetin triggered the intrinsic apoptosis pathway, demonstrated by increased mitochondrial outer membrane permeabilization (MOMP) and the release of Cytochrome c into the cytoplasm,
Cyt‑c↑,
Casp↑, which activated the caspase cascade and upregulated cleaved caspase-3, caspase-9, and PARP, ultimately leading to apoptosis [
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Apoptosis↑,
ROS↑, Moreover, ginkgetin mediated the activation of caspase cascade by the intracellular reactive oxygen species generated possibly through auto-oxidation of this biflavone, leading to apoptosis in OVCAR-3 cells
TumAuto↑, Ginkgetin induced autophagic cell death in non-small cell lung cancer (NSCLC) A549 cells
GPx4↓, Ginkgetin synergized with cisplatin to increase ferroptosis in NSCLC cells, which was confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio
xCT/SLC7A11↓,
RadioS↑, Similarly, when breast cancer cells generated radioresistance, ginkgetin promoted ferroptosis in 4T1 cells after radiotherapy by suppressing the Nrf2/HO-1 axis activity, elevating intracellular levels of reactive oxygen species (ROS) and ferrous ions
NRF2↓,
HO-1↓,
HSP90↓, MD simulations showed minimal fluctuations in the binding mode between ginkgetin and Hsp90, suggesting that ginkgetin may be an effective Hsp90 inhibitor
Dose↝, The IC50 values of ginkgetin treatment ranged from 0.58 to 150 μM, which varied due to differences in cell type, treatment time, number of plated cells, and treatment method.
Dose↝, For animal experiments, the concentration of administration ranged from 10 to 100 mg/kg, owing to different types of tumors and administration methods.
BioAv↓, Consequently, improving the bioavailability and water solubility of ginkgetin is an urgent issue that needs to be addressed
BioAv↝, In addition to considering administration routes such as intraperitoneal or intravenous injection, improvements can be made through innovative dosage form design and advanced drug delivery platforms
CYP3A4↓, research has shown that ginkgetin exhibited significant inhibition activity towards CYP3A4, which is a pivotal enzyme in the metabolic processing of many commonly used drugs, and the IC50 value was evaluated as 0.106 ± 0.004 μM
*toxicity↑, Moreover, ginkgetin induced acute kidney injury in treated mice and the main pathological lesions were confirmed in the tubule, glomeruli, and interstitium injuries
*toxicity↝, ginkgetin displayed potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressing hUGT1A1), which ...plays a crucial role in the metabolic detoxification of endogenous toxicants (e.g., bilirubin) and a variety of clinical drugs
Dose↝, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation.
toxicity↓,
PFS↓, Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival.
OS↑,
eff↑, most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival o
BioAv↑, The gossypol (−)-enantiomer—also called AT-101—is degraded more slowly and is therefore the more biologically active form
Bcl-2↓, AT-101, a natural Bcl-2 homology domain 3 (BH3) mimetic, is a small molecule inhibitor that downregulates anti-apoptotic Bcl-2 and Bcl-2-related proteins in human cancer cells
ROS↑, In addition, gossypol-induced intrinsic apoptosis might occur also as reactive oxygen species (ROS)-independent
MOMP↑, In gossypol-treated cancer cells, alterations on the mitochondrial outer membrane permeabilization (MOMP) cause the release of large amounts of apoptotic markers, such as cytochrome c and apoptosis-inducing factor (AIF),
Dose↑, Thereby, the maximum tolerated gossypol dose was determined to be 0.8 mg/kg per day (50–60 mg/day),
Casp3↑, Gossypol-induced apoptosis appears to proceed via the caspase-dependent pathway by activation of caspase-3 and caspase-9
Casp9↑,
MMP↑, as well as mitochondrial membrane depolarization
VEGF↓, suppression of vascular endothelial growth factor (VEGF) stimulating intracellular pro-angiogenic kinases phosphorylation could be inhibited by AT-101
APE1/APEX1↓, addition of gossypol leads to inhibition of APE1 and enhances the activity of cisplatin in non-small cell lung cancer
ChemoSen↑,
RadioS↑, Moreover, AT-101 was demonstrated to radiosensitize prostate cancer in vitro and in vivo without augmenting toxicity
toxicity↑, hematologic toxicities are common treatment related toxicities
AST↑, he majority of related AEs were GI and nervous system disorders, increased AST/ALT, of grade 1/2 toxicities
ALAT↑,
*toxicity↝, Our previous studies have already demonstrated that a high dose of the honokiol microemulsion (0.6 μg/mL) induces developmental toxicity in rats and zebrafish by inducing oxidative stress.
*ROS↓, In zebrafish, low doses of honokiol microemulsion (0.15, 0.21 μg/mL) significantly decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the mRNA expression of bcl-2.
*ROS↑, In contrast, high dose (0.6 μg/mL) increased the levels of ROS and MDA, decreased activities and mRNA expression of superoxide dismutase (SOD) and catalase (CAT), and increased mRNA expression of bax, c-jnk, p53 and bim.
*Dose⇅, In rat pheochromocytoma cells (PC12 cells), low doses of the honokiol microemulsion (1, 5, 10 µM) exerted a protective effect against H2O2-induced oxidative damage while high doses (≥20 µM) induced oxidative stress, which further confirms the dual ef
*BioAv↑, highly lipophilic property of honokiol allows it to readily cross the blood-brain barrier and blood-cerebrospinal fluid barrier with high bioavailability.
*BioAv↓, However, this property also limits its clinical usage due to low oral bioavailability and difficulty in intravenous administration.
*ROS⇅, levels of ROS and MDA were significantly decreased at a concentration of 0.21 μg/mL and increased at a concentration of 0.6 μg/mL in both 24 and 96 hpf embryos
*SOD↓, The activity of SOD showed only a slight reduction at 20 µM but was significantly reduced at 40 and 80 μM
*toxicity↑, According to the human rat equivalent dosage conversion, the potential toxic dose in humans may be 320 µg/kg/d
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Nor, |
MCF10 |
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BC, |
MDA-MB-231 |
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BC, |
MDA-MB-468 |
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Bxpc-3 |
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TumCP↓,
Apoptosis↑,
eff↓, cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers
*toxicity↑, normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol-induced growth inhibition.
Dose?, apigenin at 5uM promoted growth in MCF10A cells and PC3 cancer cells. This could be because polyphenols at lower concentrations are known to be associated with
cell proliferation [21], while behaving as prooxidants at high concentrations
eff↓, Apigenin- and luteolin-induced antiproliferation and apoptosis in cancer cells is inhibited by cuprous chelator but not by iron and zinc chelators
eff↓, EGCG and resveratrol, similar to that of the flavones luteolin and apigenin, also involves the mobilization of endogenous copper and consequent prooxidant effect leading to cell death.
*Inflam↓, Commercially, and in the modern apothecary, it is used for its anti-inflammatory, antiseptic, and scent properties to treat joint, ligament, and soft tissue pain.
*Pain↓,
*BioAv↝, Ten to 20 percent of MS is absorbed through the skin after application.
*BloodF↑, produces a local vasodilatory action which increases dermal blood flow, a local rise in temperature, and a sense of warmth;
*toxicity↑, Ingestion of pure oil of Wintergreen, such as in aromatherapy products, has caused poisoning and death in children due to its high concentration of MS — up to 98 percent in some products
*antiOx↑, effective antioxidant and anti-inflammatory agent
*Inflam↓,
*toxicity↑, It has been suggested that CAPE, a constituent of propolis, inhibits inducible nitric oxide synthase (iNOS) pathways which may decrease kidney perfusion and thus induce acute renal failure in at-risk patients
*Dose?, a safe dose of propolis has been reported to be 70 mg/day [27]. Interestingly, studies on pinocembrin, a component of propolis, have been conducted using 150 mg as a single dose
selectivity↑, Piperlongumine killed HNC cells regardless of p53 mutational status but spared normal cells.
eff↑, Piperlongumine increased cisplatin-induced cytotoxicity in HNC cells in a synergistic manner in vitro and in vivo.
ROS↑, Piperlongumine selectively increases ROS accumulation in HNC cells
toxicity↑, PL markedly induced death in cancer cells, while the viability of normal cells was affected only minimally at the highest concentration (15 μM) tested
GSH↓, PL decreased GSH levels and increased GSSG levels in HNC cells (Figure 2 and Supplementary Figure S1); however, PL did not increase GSSG levels in normal HOK-1 cells
GSSG↑,
*GSSG∅, however, PL did not increase GSSG levels in normal HOK-1 cells
cl‑PARP↑, PL increased the levels of PARP and PUMA proteins regardless of p53 status
PUMA↑,
GSTP1/GSTπ↓, PL regulates ROS by targeting GSTP1, a direct negative regulator of JNK [22, 23], and thereby increases JNK phosphorylation
ChemoSen↑, Piperlongumine increases the cytotoxicity of cisplatin in HNC cells in vitro and in vivo
Apoptosis↑, selenium-modified chitosan (SMC)can induce HepG2 cell apoptosis with the cell cycle arrested in the S and G2/M phases
TumCCA↑,
MMP↓, gradual disruption of mitochondrial membrane potential
Bcl-2↓, reduce the expression of Bcl2, and improve the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3
BAX↑,
cl‑Casp9↑,
cl‑Casp3↑,
Risk↓, Relevant research suggests that an inverse relationship exists between selenium intake and cancer incidence, and selenium levels are usually lower in cancer patients.
*BioAv↑, favorable biocompatibility, good bioadhesivness, and low toxicity.
*toxicity↑,
TumCG↓, Studies have found that water-soluble chitosan can significantly inhibit the growth of liver cancer cells in a dose-dependent manner
AntiTum↑, SMC has been proved to possess stronger antitumor functions and lower toxicity in cancer patients
ROS↑, SMC induced A549 cell apoptosis via a reactive oxygen species–mediated mitochondrial apoptosis pathway, which upregulated Bax and downregulated Bcl2, promoted cytochrome C release from mitochondria to cytoplasm, and activated cleaved caspase 3
Cyt‑c↑,
Fas↑, upregulating the expression levels of Fas, FasL, and Fadd,
FasL↑,
FADD↑,
Risk∅, randomized controlled studies have shown that selenium supplementation does not prevent prostate cancer (HR: 0.95; 95% CI 0.80–1.13).
ChemoSen↑, In the context of combinatorial therapy, selenium has demonstrated promising synergistic potential in the treatment of prostate cancer.
Risk↓, Moreover, there is increasing evidence suggesting that selenium can serve as a preventive agent, and the levels of selenium in the bloodstream may be linked to the development of prostate cancer
toxicity↝, Interestingly, both low and high levels of selenium have shown potential implications.
Risk↑, Generally, lower serum selenium status has been correlated with an increased risk of cancer.
eff↑, Furthermore, foundational studies have proposed that antioxidants, such as vitamin E and lycopene [50], may enhance the effectiveness of selenium in preventing the formation of mammary tumors.
*toxicity↑, selenium supplementation after diagnosis and found that supplementation of 140 μg/day or more following a nonmetastatic prostate cancer diagnosis increased prostate cancer mortality.
RadioS↑, Sodium selenite, for instance, has demonstrated a significant enhancement of the radiosensitizing effect in both HI–LAPC-4 and PC-3 xenograft tumors
eff↓, Additionally, another study [59] provided valuable evidence indicating that prostate cancer patients with low levels of selenium and lycopene are more susceptible to DNA damage induced by ionizing radiation.
eff↑, Husbeck et al. highlighted that selenite increases sensitivity to gamma radiation in prostate cancer by reducing the ratio of GSH:GSSG
ChemoSen↑, while selenium supplementation alone did not demonstrate a positive effect on prostate cancer progression, it shows promise in enhancing the efficacy of chemotherapy and radiotherapy while mitigating their associated side effects during cancer treatm
ChemoSideEff↓,
*AntiBio↑, antimicrobial and anti-inflammatory activities of the oil
*other↝, Terpinen-4-ol ≥30c 40.1%
*AntiFungal↑, TTO vapors have also been demonstrated to inhibit fungal growth
*Inflam↓, Numerous recent studies now support the anecdotal evidence attributing anti-inflammatory activity to TTO.
*ROS⇅, TTO decreases the production of reactive oxygen species by both stimulated neutrophils and monocytes and that it also stimulates the production of reactive oxygen species by nonprimed neutrophils and monocytes
*toxicity↑, TTO can be toxic if ingested, as evidenced by studies with animals and from cases of human poisoning.
Showing Research Papers: 1 to 50 of 53
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 53
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
APE1/APEX1↓, 1, NOD1↓, 1, PFS↓, 1, SUMO↓, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 1, Ferroptosis↑, 2, GPx4↓, 2, GSH↓, 3, GSSG↑, 1, GSTP1/GSTπ↓, 1, GSTs↑, 1, GSTZ1↝, 1, HO-1↓, 1, HO-1↑, 2, lipid-P↑, 1, MDA↑, 1, NRF2↓, 1, NRF2↑, 1, OXPHOS↑, 1, Prx↓, 1, PrxII↓, 1, ROS↑, 11, ROS⇅, 1, xCT/SLC7A11↓, 1,
Metal & Cofactor Biology(tgid=2) ⓘ
Ferritin↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
AIF↑, 2, ATP↓, 1, MMP↓, 3, MMP↑, 1, MPT↑, 1, mtDam↑, 2,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ALAT↑, 1, AMP↓, 1, CYP3A4↓, 1, GAPDH↓, 1, Glycolysis↓, 3, HK2↓, 2, lactateProd↓, 1, LDHA↓, 1, NADPH↓, 1, PDK1↓, 1, PI3K/Akt↓, 1, PKM2↓, 1, Warburg↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 2, p‑Akt↓, 1, Apoptosis↑, 12, BAX↑, 6, Bcl-2↓, 3, Casp↑, 4, Casp3↑, 4, cl‑Casp3↑, 4, Casp9↑, 3, cl‑Casp9↑, 2, Cyt‑c↑, 6, FADD↑, 1, Fas↑, 1, FasL↑, 1, Ferroptosis↑, 2, MAPK↓, 1, MAPK↑, 1, MOMP↑, 2, p27/CDKN1B↑, 2, PUMA↑, 1, survivin↓, 1, TumCD↑, 2,
Transcription & Epigenetics(tgid=7) ⓘ
other↝, 3,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↑, 1, ER Stress↑, 1, HSP90↓, 6,
Autophagy & Lysosomes(tgid=9) ⓘ
LC3II↑, 1, p62↓, 1, TumAuto↑, 4,
DNA Damage & Repair(tgid=10) ⓘ
p16↑, 1, P53↑, 1, cl‑PARP↑, 5, γH2AX↑, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK2↓, 1, CDK4↓, 2, cycD1/CCND1↓, 2, cycE/CCNE↓, 2, P21↑, 1, TumCCA↑, 10,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
CSCs↓, 2, EMT↓, 4, ERK↓, 1, mTOR↓, 1, NOTCH↓, 1, PI3K↓, 1, PTEN↑, 1, STAT3↓, 2, TumCG↓, 5, TumCG↑, 1, Wnt↓, 2,
Migration(tgid=13) ⓘ
E-cadherin↑, 2, p‑FAK↓, 1, MMP2↓, 4, MMP9↓, 5, N-cadherin↓, 1, TumCI↓, 4, TumCMig↓, 1, TumCP↓, 6, TumCP↑, 1, TumMeta↓, 2, TumMeta↑, 2, uPA↓, 1, Vim↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 6, EPR↑, 1, Hif1a↓, 1, VEGF↓, 4,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 1, CXCR4↓, 1, IKKα↓, 1, IL1β↓, 1, IL6↓, 1, IL8↓, 1, Imm↑, 2, Imm↝, 1, Inflam↓, 3, NF-kB↓, 6, NK cell↑, 1, TNF-α↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 2, BioAv↑, 4, BioAv↝, 4, ChemoSen↑, 10, Dose?, 1, Dose↑, 5, Dose↝, 7, eff↓, 4, eff↑, 14, eff↝, 3, Half-Life↓, 1, Half-Life↑, 1, RadioS↑, 5, selectivity↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↑, 1, AST↑, 1, Ferritin↓, 1, IL6↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 4, antiNeop↑, 1, AntiTum↑, 5, cardioP↑, 1, CardioT↑, 1, chemoP↑, 1, ChemoSideEff↓, 1, cognitive↑, 1, hepatoP↓, 1, neuroP↑, 2, NP/CIPN↑, 1, OS↑, 3, OS∅, 1, QoL↑, 1, Remission↑, 1, Risk↓, 2, Risk↑, 1, Risk∅, 1, toxicity↓, 7, toxicity↑, 23, toxicity↝, 3, toxicity∅, 1,
Total Targets: 165
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiBio↑, 2,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 5, Catalase↓, 1, Catalase↑, 1, GSH↑, 1, GSSG∅, 1, HDL↑, 1, lipid-P↓, 1, NADPH/NADP+↑, 1, ROS↓, 4, ROS↑, 3, ROS⇅, 2, SOD↓, 2, SOD↑, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
12LOX↓, 1, BUN↑, 1, glucoNG↓, 1, Glycolysis↑, 1, LDL↓, 1, NH3↑, 1,
Cell Death(tgid=5) ⓘ
iNOS↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other?, 1, other↑, 2, other↝, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
NO↑, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 2,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 2, IL6↑, 1, Inflam↓, 9, Inflam↑, 1, NF-kB↓, 2, PGE2↓, 1, TNF-α↓, 1,
Synaptic & Neurotransmission(tgid=18) ⓘ
BDNF↑, 1, GABA↑, 1, tau↓, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 1, NLRP3↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 4, BioAv↑, 5, BioAv↝, 1, Dose?, 1, Dose↓, 1, Dose↑, 3, Dose⇅, 1, Dose↝, 6, eff↑, 1, Half-Life↓, 1,
Clinical Biomarkers(tgid=22) ⓘ
BloodF↑, 1, creat↑, 2, IL6↑, 1,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, cardioP↑, 2, chemoP↑, 1, cognitive↑, 1, memory↑, 2, neuroP↑, 3, Pain↓, 1, Strength↑, 1, toxicity↓, 3, toxicity↑, 29, toxicity↝, 4,
Infection & Microbiome(tgid=24) ⓘ
AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 2,
Total Targets: 66
Scientific Paper Hit Count for: toxicity, toxicity
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#:1025 State#:% Dir#:2
wNotes=on sortOrder:rid,rpid
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