toxicity Cancer Research Results
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Scientific Papers found: Click to Expand⟱
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
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↓,
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↑, 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↓,
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↑, 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
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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↓,
*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↝, 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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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.
*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↓,
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TumCP↓, The IC50 of TF in the treatment of 8305C cells for 48 h was 21.79 µg/mL. TF inhibited the proliferation, migration, and invasion of the 8305C cells at a concentration of 1/2 IC50, and induced the apoptosis of the 8305C cells
TumCMig↓,
TumCI↓,
Apoptosis↑,
Casp3↑, TF significantly increased the expression of the caspase3, caspase8, and caspase9 proteins in vivo and in vitro, and significantly inhibited the expression of the survivin protein.
Casp8↑,
Casp9↑,
survivin↓,
SREBP1↓, TF also inhibited the messenger RNA (mRNA) expression of SREBP1 and PPARD,
toxicity↑, TF exhibits potent anti-ATC efficacy with no observable toxicity which is a new advantage of TF in the treatment of ATC.
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p‑PDH↓, Both thiamine and DCA reduced the extent of PDH phosphorylation, reduced glucose consumption, lactate production, and mitochondrial membrane potential.
GlucoseCon↓, High dose thiamine reduces glucose consumption and lactate production
lactateProd↓,
MMP↓,
Casp3↑, High dose thiamine and DCA did not increase ROS but increased caspase-3 activity
eff↑, Our findings suggest that high dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate
PDKs↓,
selectivity↑, An advantage to targeting PDK activity is that overexpression of PDKs and extensive phosphorylation of PDH is found in cancer cells and not in normal tissue [14]. This may provide for selective targeting towards malignant tissue
TumCG↓, thiamine suppressed tumor growth at doses greater than 75 times the recommended daily intake
Dose∅, IC50 of thiamine was lower than DCA for both cell lines with values of 4.9 for SK-N-BE and 5.4 mM for Panc-1.
MMP↓, decrease in mitochondrial membrane potential
ROS∅, cells treated with thiamine or DCA were assayed for peroxide following 30 min, 1 h, and 2 h of treatment. No significant change in ROS was observed over all time
toxicity↑, Smithline et al. reported no adverse effects in healthy patients who were given 1.5g/day of thiamine [34]. Only minor side effects, such as nausea and indigestion were reported in patients given doses as high as 7.5 g/day
antiOx↑, Free thiamine has direct antioxidant properties
*ER Stress↓, protective effect of vitamin K on blood vessels, by reducing inflammation and stress ER
*toxicity↓, Natural forms of vitamin K–K1 and K2—have only a low potential for toxicity
*toxicity↑, However, K3 may demonstrate harmful potential: synthetic vitamin K3 can lead to liver damage
ROS↑, Like another quinone, doxorubicin, menadione exerts its cytotoxic effects by stimulating the generation of oxidative stress, leading to DNA damage
PI3K↑, In bladder cancer cells (T24), vitamin K2 significantly induces PI3K/Akt phosphorylation and increases expression of HIF-1α, intensifying glucose consumption and lactate formation.
Akt↑,
Hif1a↑,
GlucoseCon↑,
lactateProd↑,
ChemoSen↑, Numerous studies indicate that the K vitamins have an additive or synergistic effect on various chemotherapeutic agents.
eff↑, A strong synergism between K1 and sorafenib has been demonstrated in numerous studies
eff↑, ascorbic acid (AA), has a synergistic effect on K3 [73,122,123]. The AA/K3 association leads to an excessive increase in oxidative stress and a decrease in the potential of the mitochondrial membrane, which is a crucial trigger of tumor cell death
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:
Redox & Oxidative Stress ⓘ
antiOx↑, 1, Ferroptosis↑, 1, GPx4↓, 1, GSH↓, 2, GSSG↑, 1, GSTP1/GSTπ↓, 1, GSTs↑, 1, HO-1↑, 2, NRF2↑, 1, Prx↓, 1, PrxII↓, 1, ROS↑, 6, ROS⇅, 1, ROS∅, 1,
Metal & Cofactor Biology ⓘ
Ferritin↓, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 1, MMP↓, 4, mtDam↑, 1,
Core Metabolism/Glycolysis ⓘ
AMP↓, 1, GAPDH↓, 1, GlucoseCon↓, 1, GlucoseCon↑, 1, Glycolysis↓, 2, HK2↓, 1, lactateProd↓, 1, lactateProd↑, 1, NADPH↓, 1, p‑PDH↓, 1, PDKs↓, 1, PI3K/Akt↓, 1, SREBP1↓, 1,
Cell Death ⓘ
Akt↓, 1, Akt↑, 1, Apoptosis↑, 6, BAX↑, 4, Bcl-2↓, 2, Casp↑, 1, Casp3↑, 3, cl‑Casp3↑, 2, Casp8↑, 1, Casp9↑, 2, cl‑Casp9↑, 1, Cyt‑c↑, 3, FADD↑, 1, Fas↑, 1, FasL↑, 1, Ferroptosis↑, 1, p27↑, 1, PUMA↑, 1, survivin↓, 2, TumCD↑, 1,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, ER Stress↑, 1, HSP90↓, 2,
Autophagy & Lysosomes ⓘ
LC3II↑, 1, p62↓, 1, TumAuto↑, 2,
DNA Damage & Repair ⓘ
p16↑, 1, cl‑PARP↑, 2,
Cell Cycle & Senescence ⓘ
CDK4↓, 1, cycD1/CCND1↓, 1, cycE/CCNE↓, 1, TumCCA↑, 5,
Proliferation, Differentiation & Cell State ⓘ
CSCs↓, 1, EMT↓, 1, ERK↓, 1, mTOR↓, 1, PI3K↑, 1, STAT3↓, 1, TumCG↓, 6, Wnt↓, 1,
Migration ⓘ
E-cadherin↑, 1, MMP2↓, 1, MMP9↓, 3, TumCI↓, 3, TumCMig↓, 1, TumCP↓, 3, TumMeta↓, 1, uPA↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 3, Hif1a↓, 1, Hif1a↑, 1, VEGF↓, 2,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, CXCR4↓, 1, IKKα↓, 1, IL1β↓, 1, IL6↓, 1, IL8↓, 1, Imm↑, 1, Imm↝, 1, Inflam↓, 1, NF-kB↓, 4, NK cell↑, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↑, 1, BioAv↝, 3, ChemoSen↑, 5, Dose?, 1, Dose↝, 2, Dose∅, 1, eff↓, 4, eff↑, 12, eff↝, 2, Half-Life↓, 1, RadioS↑, 2, selectivity↑, 2,
Clinical Biomarkers ⓘ
Ferritin↓, 1, IL6↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 1, AntiTum↑, 2, CardioT↑, 1, ChemoSideEff↓, 1, cognitive↑, 1, hepatoP↓, 1, neuroP↑, 1, OS↑, 2, OS∅, 1, QoL↑, 1, Risk↓, 2, Risk↑, 1, Risk∅, 1, toxicity↓, 4, toxicity↑, 11, toxicity↝, 2, toxicity∅, 1,
Total Targets: 128
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 3, Catalase↑, 1, GSH↑, 1, GSSG∅, 1, lipid-P↓, 1, NADPH/NADP+↑, 1, ROS↓, 2, ROS↑, 1, ROS⇅, 1, SOD↓, 1, SOD↑, 1,
Mitochondria & Bioenergetics ⓘ
ATP↓, 1,
Core Metabolism/Glycolysis ⓘ
12LOX↓, 1, glucoNG↓, 1, Glycolysis↑, 1, NH3↑, 1,
Protein Folding & ER Stress ⓘ
ER Stress↓, 1,
Angiogenesis & Vasculature ⓘ
NO↑, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, IL6↑, 1, Inflam↓, 3, TNF-α↓, 1,
Synaptic & Neurotransmission ⓘ
BDNF↑, 1, tau↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 3, BioAv↑, 3, Dose?, 1, Dose↑, 1, Dose⇅, 1, Dose↝, 2, eff↑, 1,
Clinical Biomarkers ⓘ
IL6↑, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, cognitive↑, 1, memory↑, 1, neuroP↑, 2, Strength↑, 1, toxicity↓, 1, toxicity↑, 14, toxicity↝, 2,
Total Targets: 42
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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