mtDam Cancer Research Results
mtDam, mitochondrial damage: Click to Expand ⟱
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Mitochondrial damage can lead to a shift from oxidative phosphorylation to glycolysis, a process known as the Warburg effect. This shift can provide cancer cells with a selective advantage, allowing them to grow and proliferate more rapidly.
Mitochondrial Damage can also lead to cell death of cancer cells.
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Scientific Papers found: Click to Expand⟱
selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear.
Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines
(Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as
well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase
arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of
Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.
mtDam↑, 3-BromoPyruvate severely damaged mitochondrial integrity which might have severely affected ATP generation in cancer cells.
HK2↓, 3-BP inhibits hexokinase II (HK2) and TGFbeta1 and enhanced active caspase-3 expression in tumor tissues as compared to untreated control.
TGF-β↓,
Casp3↑,
selectivity↑,
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP
other↝, Since the use of ALA-based drugs for tumor diagnosis or therapy depends on preferential PpIX tumor accumulation, we begin this review with an overview of PpIX biosynthesis from ALA and end with the prospect of combining the diagnostic and therapeutic
ROS↑, These components individually are not harmful but become cytotoxic when combined due to the generation of reactive oxygen species (ROS) via type I and II photochemical reactions.
other↝, ALA was known to cause endogenous PpIX accumulation in human lymphocytes in the 1970s [15].
mtDam↑, which causes direct mitochondrial structural damage and Ca2+ release [24].
Ca+2↑,
ER Stress↑, ALA-PDT is known to damage the endoplasmic reticulum (ER) and cause Ca2+ release, triggering apoptosis through ER-stress signaling [25].
Apoptosis↑,
TumAuto↑, Lastly, ALA-PDT is also known to induce autophagy, the degradation of cellular components by lysosomes.
other↝, ALA administration exhibits red fluorescence and photosensitizing activity upon light activation.
Dose↝, Although blue and red light-emitting diode (LED) illuminators are commonly used as the light source to activate ALA and MAL for PDT of AK lesions, natural daylight is emerging as an attractive and convenient alternative.
Imm↑, ALA-PDT not only directly kills tumor cells but also elicits potent immune responses with important implications in the long-term therapeutic outcome.
OS↑, Results indicate that the AgNPs were efficient in prolongation of life span, reduction of tumor volume and body weight in tumor animals.
TumVol↓,
Weight↑,
AntiTum↑, AgNPs are potent in antitumor activity and the molecular mechanism is by the induction of apoptosis through the mitochondrial dependent and independent pathways.
Apoptosis↑,
mtDam↑,
AntiCan↑, AgNPs exert potent anticancer effects against colon cancer cell lines primarily by inducing cell death through mechanisms including reactive oxygen species (ROS) generation
ROS↑,
mtDam↑, mitochondrial dysfunction, and apoptosis modulation, leading to significant reductions in cell viability.
tumCV↓,
selectivity↑, effectively targeting cancer cells while sparing healthy counterparts, thereby emphasizing their safety profile and potential for minimizes ng systemic toxicity.
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in-vitro, |
Pca, |
PC3 |
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in-vitro, |
Pca, |
LNCaP |
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in-vitro, |
Pca, |
DU145 |
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selectivity↑, Both AgNPs and G-AgNPs were cytotoxic only to CRPC cells and not to hormone-sensitive ones and their effect was higher after functionalization showing the potential of glucose to favor AgNPs’ uptake by cancer cells.
ROS↑, NPs increased the ROS, inducing mitochondrial damage, and arresting cell cycle in S Phase, therefore blocking proliferation, and inducing apoptosis.
mtDam↑,
TumCCA↑,
TumCP↓,
Apoptosis↑,
MMP↓, AgNPs were able to depolarize the cells’ mitochondria to 32.74% and 10.36%, respectively
ROS↑,
DNAdam↑,
Apoptosis↑,
mtDam↑,
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in-vitro, |
PC, |
Bxpc-3 |
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in-vitro, |
PC, |
PANC1 |
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in-vitro, |
PC, |
MIA PaCa-2 |
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in-vivo, |
NA, |
NA |
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mtDam↑, in cancer cells only. ALA protected normal cells
ROS↑, in cancer cells only. ALA protected normal cells
*toxicity↓, Nonmalignant CRL-4023 and LX-2 cells were treated with α-lipoic acid at concentrations of 0.5 mM, 1 mM, 2 mM and 3 mM, Both cell lines were largely resistant to any concentration
Dose∅, ALA dose: we used α-lipoic acid concentrations of 0.5 and 1 mM
selectivity↑, higher sensitivity of malignant cells to AgNPs.
Apoptosis↑,
ROS↑,
LDH↓, leakage of lactate dehydrogenase (LDH);
TNF-α↑,
mtDam↑,
TumAuto↑,
Casp3↑,
Casp9↑,
DNAdam↑, induced DNA-fragmentation
GRP78/BiP↑, AgNP treatment induced the expression of ER chaperons Grp94 and Grp78/Bip,
ER Stress↑, depleted endoplasmic reticulum (ER) calcium stores, caused notable ER stress and decreased plasma membrane positioning of Pgp
ROS↑,
mtDam↑,
ROS↑,
mtDam↑,
mtDam↑,
LDH↓, LDH leakage also increased in all cell lines exposed to AgNPs
ROS↑,
mtDam↑,
TumCG↓,
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in-vitro, |
Lung, |
A549 |
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in-vitro, |
Lung, |
L132 |
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mtDam↑,
ROS↑,
Hif1a↑, HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions
HIF-1α knockdown enhances hypoxia induced decrease in cell viability
LC3s↑,
p62↑,
eff↓, Hypoxia decreases the effects of anticancer drugs in solid tumor cells through the regulation of HIF-1α
mtDam↑,
ROS↑,
TumCCA↑,
Casp3↑,
BAX↑,
Bcl-2↓,
P53↑,
LDH↓, When the cells were treated with AgNPs and AgNO3, the amount of LDH leaked into the media increased in a dose-dependent manner
ROS↑,
mtDam↑,
DNAdam↑,
P53↑,
P21↑,
BAX↑,
Casp3↑,
Bcl-2↓,
Casp9↑,
Nanog↓,
OCT4↓,
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CardioV, |
NA |
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Review, |
AD, |
NA |
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*Inflam↓, allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others).
*antiOx↑, improving the antioxidant system
*neuroP↑,
*cardioP↑,
*AntiTum↑,
*mtDam↑, Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes.
*HSP70/HSPA5↑, llicin improves mitochondrial function by enhancing the expression of HSP70 and decreasing RAAS activation
*NRF2↑,
*RAAS↓,
*cognitive↑, Allicin enhances the cognitive function of APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice by decreasing the expression levels of Aβ, oxidative stress, and improving mitochondrial function.
*SOD↑, positive effects on cognition in an AD mouse model by administrating a preventive dose of allicin. These effects might be mediated by an increase of SOD and reduction of ROS
*ROS↓,
*NRF2↑, Chronic treatment with allicin increased the expression of NRF2 and targeted downstream of NRF2, such as NADPH, quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (γ-GCS), in the hippocampus of aged mice
*ER Stress↓, protective effects of 16 weeks of allicin treatment in a rat model of endoplasmic reticulum stress-related cognitive deficits.
*neuroP↑, allicin was able to ameliorate depressive-like behaviors by decreasing neuroinflammation, oxidative stress iron
aberrant accumulation,
*memory↑, allicin improved lead acetate-caused learning and memory deficits and decreased the ROS level
*TBARS↓, Oral administration of allicin was able to reduce thiobarbituric reactive substances (TBARS) and
myeloperoxidase (MPO) levels, and concurrently increased (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in a rat model of
*MPO↓,
*SOD↑,
*GSH↑,
*iNOS↓, decreasing the expression of iNOS and increased the phosphorylation of endothelial NOS (eNOS)
*p‑eNOS↑,
*HO-1↑, OSCs upregulate the endogenous antioxidant NRF2 and heme oxygenase-1 (HO-1)
TumCG↓, Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase
TumCCA↑,
MMP↓, decreased mitochondrial membrane potential of the treated cells
ROS↑, Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells.
Ca+2↑,
ER Stress↑,
mtDam↑, together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.
CHOP↑,
DR5↑,
cl‑BID↑,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
Apoptosis↑,
CSCs↓,
mtDam↑, inducing mitochondrial dysfunction.
TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.
*ROS↓, normal cells
*MDA↓, normal cells
*TNF-α↓, normal cells
*TGF-β↓, TGF-β1 normal cells
*IL10↑, normal cells
ROS↑, cancer cells
DNAdam↑, cancer cells
mtDam↑, cancer cells
MMP↓, cancer cells
Apoptosis↑, cancer cells
TumCCA↑, cancer cells
Hif1a↓, cancer cells
VEGF↓, cancer cells
RadioS↑, revealed radiosensitizing properties
ACLY↓, Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells
PD-L1↑,
mtDam↑, Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway.
cGAS–STING↑, ACLY inhibition leads to cGAS-STING activation
LDL↓, bempedoic acid (BemA; also named ETC-1002) has been recently approved by U.S. Food and Drug Administration (FDA) for lowering low-density lipoprotein cholesterol
eff↑, dietary PUFA supplementation is sufficient to mimic the enhanced efficacy of PD-L1 blockade by ACLY inhibition, providing promising combinational strategies for immunotherapy-resistant tumors therapy.
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
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Cerv, |
HeLa |
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in-vitro, |
lymphoma, |
U937 |
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mtDam↑, It was shown to induce apoptosis via a direct effect on mitochondria.
TumAuto↑, autophagy is activated as a response to the mitochondrial damage inflicted by BetA
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in-vitro, |
CRC, |
T24/HTB-9 |
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Bladder, |
UMUC3 |
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Bladder, |
5637 |
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TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB/CCNB1↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1/CCNA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,
AntiCan↑, Borneol is a multifaceted anticancer agent with intrinsic cytotoxic activity;
Apoptosis↑, via diverse mechanisms such as apoptosis induction, mitochondrial dysfunction, ROS generation
mtDam↑,
ROS↑,
mTORC1↓, and inhibition of oncogenic pathways, including mTORC1/eIF4E/HIF-1α, NF-κB, STAT3, and PI3K/Akt.
EIF4E↓,
Hif1a↓,
NF-kB↓,
STAT3↓,
PI3K↓,
Akt↓,
ChemoSen↑, borneol demonstrates significant synergistic effects when combined with established chemotherapeutic agents like temozolomide, doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil,
BioEnh↑, enhancing drug uptake, overcoming resistance, and amplifying apoptosis, especially in drug-resistant and brain tumor models.
BioAv↑, borneol possesses high intestinal absorption, BBB permeability, moderate toxicity, and compliance with Lipinski's Rule of Five.
BBB↑,
toxicity↝,
GutMicro↑, Butyrate, a short-chain fatty acid, is generated through gut microbial fermentation of dietary fiber.
*Inflam↓, Butyrate, a primary anti-inflammatory SCFA, exhibits a multifaceted role in mitigating inflammation
*IL6↓, It inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, TNF-α and IL-17, which helps to prevent colon cancer
*TNF-α↓,
*IL17↓,
*IL10↑, while promoting IL-10 production
*ROS↝, regulates the production of reactive oxygen species (ROS)
COX2↓, butyrate has been observed to suppress inflammation by inhibiting the expression of cyclooxygenase-2 mRNA in colonic tissues (60).
NLRP3↓, butyrate exhibits the highest efficiency in the negative regulation of NLRP3
Imm↑, Enhancement of the immunotherapeutic effect
HDAC↓, Inhibition of HDAC activity in cells
TumCCA↑, Butyrate has been found to induce cell cycle arrest in the G0/G1 phase in a dose-dependent manner in vitro in numerous tumors, including colon, liver, lung and bladder cancer,
Apoptosis↑, butyrate-induced apoptosis is accompanied by elevated ROS levels and caspase activity (126)
ROS↑,
Casp↑,
mtDam↑, suggests that ROS can induce mitochondrial membrane damage, release Cyt c from damaged mitochondria, and enhance apoptosis via the Cyt c/caspase-3 pathway
Cyt‑c↑,
eff↑, Clostridium butyricum is an anaerobic bacterium classified as a probiotic due to its production of butyric acid (139)
chemoP↑, butyrate not only alleviates the side effects associated with conventional chemotherapeutic agents such as oxaliplatin, irinotecan and 5-fluorouracil (149-151), but it also enhances the efficacy of both chemotherapy and immunotherapy
ChemoSen↑,
eff↑, metformin has been demonstrated to enhance the biosynthesis of butyrate while concurrently inhibiting the progression of CRC
RadioS↑, Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone.
HCAR2↑, Activation of cell-surface receptors (GPR41, GPR43 and GPR109A);
TRPV1↑, we reported that capsaicin (CAP), a transient receptor potential vanilloid type1 (TRPV1) agonist, inhibited the viability of anaplastic thyroid cancer cells.
tumCV↓,
Ca+2↑, Capsaicin treatment triggered Ca2+ influx by TRPV1 activation, resulting in disequilibrium of intracellular calcium homeostasis.
mtDam↑, In addition, the disruption of mitochondrial calcium homeostasis caused by capsaicin led to mitochondrial dysfunction in ATC cells
ROS↑, as evidenced by the production of mitochondrial reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), and opening of mitochondrial permeability transition pore (mPTP)
MMP↓,
MPT↑,
Cyt‑c↑, the resulting release of cyt c into the cytosol triggered apoptosome assembly and subsequent caspase activation and apoptosis.
Casp↑,
Apoptosis↑,
*antiOx↑, antioxidant (8), anti-inflammatory (9) and anti-obesity (10) properties.
*Inflam↓,
*Obesity↓,
chemoPv↑, Many laboratories have reported that capsaicin possesses chemopreventive and chemotherapeutic effects
Apoptosis↑, Capsaicin has been shown to induce apoptosis in many different types of cancer cell lines including pancreatic (19) colonic (24), prostatic (25), liver (26), esophagieal (27), bladder (28), skin (29), leukemia (30), lung (31), and endothelial cells (
selectivity↑,
TRPV1↑, Transient receptor potential vanilloids (TRPVs) are receptors of capsaicin which lead to Ca2+-mediated mitochondrial damage and cytochrome c release.
Ca+2↑,
mtDam↑,
Cyt‑c↑,
P53↑, Capsaicin was found to induce p53 phosphorylation at the Ser-15 residue (30) and enhanced p53 acetylation through down-regulation of sirtuin 1 (
SIRT1↓,
TumCCA↑, Capsaicin induced G0/G1 phase arrest in human esophageal carcinoma cells with an increase of p21 and a decrease of CDK4, CDK6 and cyclin E (
P21↑,
CDK4↓,
CDK6↓,
cycE/CCNE↓,
angioG↓, Capsaicin has anti-angiogenic properties both in vitro and in vivo
TumMeta↓, Capsaicin treatment significantly reduced the metastatic burden in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (57).
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Melanoma, |
B16-F10 |
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NA, |
NA, |
A375 |
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ROS↑, Oregano extract induced oxidative stress and inhibited melanogenesis and tumor cell proliferation, triggering programmed cell death pathways (both apoptosis and necroptosis) through mitochondria and DNA damage.
TumCP↓,
Apoptosis↑,
Necroptosis↑,
mtDam↑,
DNAdam↑,
selectivity↑, By contrast, oregano extract was safe on healthy tissues, revealing no cytotoxicity and mutagenicity on C2C12 myoblasts
Dose↝, Thymol 16.64%, Carvacrol 34.82%
MPT↓, Mitochondrial membrane permeability loss suggested mitochondrial damage and apoptosis induction.
Apoptosis↑, Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress.
PPARγ↓,
mtDam↑,
ROS↑, Induced cell death via apoptosis and increased ROS levels.
EMT↓, It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity.
CD8+↑,
NK cell↑,
ChemoSen↑, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
ATP↓, CBD decreases intracellular ATP and glucose levels
glucose↓,
Ca+2↑, CBD enhances calcium influx (mediated by TRPV2) and elevates p-ERK expression in CIK cells
TRPV2↑,
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↓,
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Review, |
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Review, |
Diabetic, |
NA |
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Review, |
AD, |
NA |
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Review, |
Park, |
NA |
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Stroke, |
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*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms
TumCP↓, significantly suppressing cell proliferation, migration, colony formation, and invasion while inhibiting the epithelial–mesenchymal transition.
TumCMig↓,
TumCI↓,
EMT↓, CGA Inhibits Migration, Epithelial–Mesenchymal Transition, Invasion, and Colony Formation of RBE Cells
Apoptosis↑, CGA induced apoptosis, modulated cell cycle progression
TumCCA↑,
AKR1B10↓, CGA treatment reduced AKR1B10 expression.
Akt↓, reducing AKR1B10 levels, thereby suppressing AKT activation.
mtDam↑, CGA Promotes Mitochondrial Damage and Apoptosis in RBE Cells
BAX↑, CGA significantly increased the expression levels of bax, caspase9, and caspase3 in the RBE cells while decreasing the expression level of bcl-2
Casp9↑,
Casp3↑,
Bcl-2↓,
| - |
in-vitro, |
Lung, |
A549 |
|
|
|
- |
in-vitro, |
Liver, |
HepG2 |
|
|
|
EPR↑, A-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS).
mtDam↑,
ROS↑,
Apoptosis↑, Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells.
| - |
in-vitro, |
Ovarian, |
SKOV3 |
|
|
|
- |
in-vitro, |
Ovarian, |
A2780S |
|
|
|
- |
in-vitro, |
Nor, |
HEK293 |
|
|
|
Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII
↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo
eff↑, generate a large number of reactive oxygen species (ROS) when exposed to light, which could be adopted for photodynamic therapy.
Fenton↑, Cu2+ is vulnerable to the reduction to Cu+, allowing Cu to drive the Fenton reaction and produce hydroxyl radicals (·OH).
ROS↑, increasing Cu ions in cancer tissue makes an antitumor impact that mainly involves OS by triggering the Fenton reaction, which can produce ROS
eff↑, compared with other metals (iron, chromium, cobalt and nickel), the Cu-based Fenton reaction can react in wider pH range
mtDam↑, Excessive Cu can induce the toxic level of ROS that may aggravate the mitochondrial ROS, causing mitochondrial damage
BAX↑, Cu-induced ROS increased Bax (pro-apoptotic protein), while Bcl2 (anti-apoptotic protein) was decreased
Bcl-2↓,
MMP↓,
Cyt‑c↑, releasing CytC that activated Caspase3
Casp3↑,
ER Stress↑, Nano-CuO) triggers OS by ROS, thus stimulating endoplasmic reticulum (ER)-stress
CHOP↑, which thereby enhanced the expression of CHOP
Apoptosis↑, and CHOP-induced apoptosis
selectivity↑, In fact, autophagy induced by copper can either protect cells from death or contribute to cell death, depending on autophagic flux, which is associated with the concentration of copper.
eff↑, combining artemisinin (ART) and copper peroxide nanodots to enhance autophagy and ferroptosis that produced highly cancer toxic reaction
Pyro↑, Copper-Based Pyroptosis
Paraptosis↑, Copper-Based Paraptosis
Cupro↑, Copper-Based Cuproptosis
ChemoSen↑, studies suggested that Cu-MOFs might be a robust nanoplatform for enhancing chemotherapy activity of Cu-organic compounds.
eff↑, CuS NPs had the ability to directly target cancer cells and then induce in nucleus by modification of RGD and TAT peptides, thus heating cancer cell to exhaustive apoptosis through 980 nm NIR irradiation
| - |
vitro+vivo, |
Lung, |
A549 |
|
|
|
- |
vitro+vivo, |
Lung, |
H1299 |
|
|
|
TumAuto↑,
TumCG↓,
TumCP↓,
Iron↑, iron overload
GSH↓, GSH depletion
lipid-P↑, accumulation of intracellular iron and lipid‐reactive oxygen species (ROS), lipid peroxidation
GPx↓, GPX4
mtDam↑, mitochondrial membrane rupture
autolysosome↑,
Beclin-1↑,
LC3s↑,
p62↓,
Ferroptosis↑, via activating autophagy
| - |
in-vitro, |
Liver, |
A549 |
|
|
|
- |
in-vitro, |
Pca, |
PC3 |
|
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- |
in-vitro, |
AML, |
HL-60 |
|
|
|
GSH↓, depletion
mtDam↑, mitochondrial dysfunction
MMP↓,
Cyt‑c↑,
TumCMig↓,
TumCP↓,
ROS↑,
mtDam↑,
DNAdam↑,
Apoptosis↑,
ATR↑,
P21↑,
p‑P53↑,
GADD45A↑,
p‑γH2AX↑,
*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,
selectivity↑, We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells
TumCD↑,
TumCMig↓,
TumCI↓,
angioG↓,
mtDam↑, Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death.
Iron↑,
lipid-P↑,
Ferroptosis↑,
NF-kB↑, Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu.
p‑p62↑, DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2.
Keap1↓,
eff↑, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis
eff↓, Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu.
ChemoSen↑, Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase.
H2O2↑,
Fenton↑,
PDGFR-BB↑,
EGFR↓, EGCG inhibits activities of EGFR, VEGFR, and IGFR
VEGFR2↓,
IGFR↓,
Ca+2↑, EGCG elevates cytosolic Ca2+ levels
NO↑, EGCG-stimulated elevation of cytosolic calcium contributes to NO production by binding to calmodulin
Sp1/3/4↓,
NF-kB↓,
AP-1↓,
STAT1↓,
STAT3↓,
FOXO↓, FOXO1
mtDam↑,
TumAuto↑,
| - |
Review, |
BC, |
MCF-7 |
|
|
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- |
Review, |
BC, |
MDA-MB-231 |
|
|
|
HER2/EBBR2↓,
EGFR↓,
mtDam↑,
ROS↑,
PI3K/Akt↓,
P53↑,
P21↑,
Casp3↑,
Casp9↑,
BAX↑,
PTEN↑,
Bcl-2↓,
hTERT/TERT↓,
STAT3↓,
TumCCA↑, EGCG causes cell cycle arrest by preventing cyclin accumulation D1
Hif1a↓,
| - |
in-vitro, |
CRC, |
HCT116 |
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- |
in-vitro, |
CRC, |
HT29 |
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- |
in-vitro, |
Liver, |
HepG2 |
|
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- |
in-vitro, |
Liver, |
HUH7 |
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|
|
tumCV↓, EGCG treatment decreased cell viability and increased mitochondrial damage‐triggered apoptosis in both HCT116 and HT‐29 cancer cells
mtDam↑,
Apoptosis↑,
ATP↓, Suppression of ATP synthesis by EGCG
lipoGen↓, depletion of lipogenesis in the DNL pathway,
eff↑, Antiproliferative activity of EGCG and 5FU reduces tumor progression in a nude mouse xenograft model
*Dose↓, Low intensity electric fields appear to enhance cell function.
Apoptosis↑, Here we focus on high electric fields that induce programmed cell death or apoptosis in cells and tumors in mice.
DNAdam↑, Mitochondria, and probably nucleus/DNA and membrane pump mechanisms, are intracellular targets that contribute to cell death.
mtDam↑,
Ca+2↑, Ca2+ overload→ATP depletion→mitochondrial dysfunction
ATP↓,
mtDam↑,
ROS↑, ROS generation from mitochondrial leakage disrupts cell homeostasis.
CellMemb↑, EP: membrane permeabilization→drug uptake↑;
tyrosinase↓,
CK2↓,
TumCP↓,
TumCMig↓,
FGF↓,
FGFR1↓,
PI3K↓,
Akt↓,
VEGF↓,
FGFR1↓,
FGFR2↓,
PDGF↓,
ALAT↓,
AST↓,
TumCCA↑, G0/G1 phase arrest
CDK2↓,
CDK4↓,
CDK6↓,
BAX↓,
Bcl-2↓,
MMP2↓,
MMP9↓,
P53↑,
PARP↑,
PUMA↑,
NOXA↑,
Casp3↑,
Casp9↑,
TIMP1↑,
lipid-P↑,
mtDam↑,
EMT↓,
Vim↓,
E-cadherin↓,
p‑STAT3↓,
COX2↓,
CDC25↓,
RadioS↑,
ROS↑,
DNAdam↑,
γH2AX↑,
PTEN↑,
LC3II↓,
Beclin-1↓,
SOD↓,
Catalase↓,
GPx↓,
Fas↑,
*BioAv↓, ferulic acid stability and limited solubility in aqueous media continue to be key obstacles to its bioavailability, preclinical efficacy, and clinical use.
cMyc↓,
Beclin-1↑, ferulic acid by elevating the levels of the apoptosis and autophagy biomarkers, including beclin-1, Light chain (LC3-I/LC3-II), PTEN-induced putative kinase 1 (PINK-1), and Parkin
LC3‑Ⅱ/LC3‑Ⅰ↓,
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↓,
Showing Research Papers: 1 to 50 of 87
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 87
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned ⓘ
AKR1B10↓, 1,
Redox & Oxidative Stress ⓘ
Catalase↓, 1, Fenton↑, 3, Ferroptosis↑, 3, GPx↓, 3, GPx4↓, 1, GSH↓, 6, H2O2↑, 2, HO-1↑, 3, Iron↑, 4, Keap1↓, 1, lipid-P↑, 4, MDA↑, 1, NADPH/NADP+↓, 1, NRF2↑, 1, mt-OXPHOS↓, 1, Prx↓, 1, PrxII↓, 1, ROS↓, 1, ROS↑, 35, ROS∅, 1, SOD↓, 1,
Metal & Cofactor Biology ⓘ
FTH1↓, 1, NCOA4↑, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 7, CDC25↓, 2, FGFR1↓, 2, mitResp↓, 1, MMP↓, 10, MPT↓, 1, MPT↑, 1, mtDam↑, 49,
Core Metabolism/Glycolysis ⓘ
ACLY↓, 1, ALAT↓, 1, AMPK↑, 1, cMyc↓, 3, GAPDH↓, 1, glucose↓, 1, GlucoseCon↓, 1, Glycolysis↓, 4, HK2↓, 4, lactateProd↓, 2, LDH↓, 3, LDL↓, 1, lipoGen↓, 1, NADPH↓, 1, PFKP↓, 1, PI3K/Akt↓, 1, PPARγ↓, 1, Pyruv↓, 1, SIRT1↓, 1,
Cell Death ⓘ
Akt↓, 8, p‑Akt↓, 1, Apoptosis↑, 25, Bak↑, 1, BAX↓, 1, BAX↑, 9, Bax:Bcl2↑, 1, Bcl-2↓, 10, Bcl-xL↓, 1, BID↑, 1, cl‑BID↑, 1, BIM↑, 1, Casp↑, 4, Casp3↑, 15, cl‑Casp3↑, 1, Casp8↑, 1, cl‑Casp8↑, 1, Casp9↑, 10, cl‑Casp9↑, 1, CK2↓, 1, Cupro↑, 1, Cyt‑c↑, 12, Diablo↑, 1, DR5↑, 1, Fas↑, 1, Ferroptosis↑, 3, hTERT/TERT↓, 1, JNK↑, 1, p‑JNK↑, 1, MAPK↓, 1, Mcl-1↓, 2, Necroptosis↑, 1, NOXA↑, 1, p27↑, 1, Paraptosis↑, 1, PUMA↑, 1, Pyro↑, 1, TRPV1↑, 2, TumCD↑, 2,
Kinase & Signal Transduction ⓘ
CaMKII
↓, 1, HCAR2↑, 1, HER2/EBBR2↓, 1, Sp1/3/4↓, 1, TRPV2↑, 1,
Transcription & Epigenetics ⓘ
cJun↓, 1, other↝, 3, tumCV↓, 3,
Protein Folding & ER Stress ⓘ
ATF6↑, 1, CHOP↑, 4, ER Stress↑, 8, GRP78/BiP↑, 2, HSF1↓, 1, HSP90↓, 1, IRE1↑, 1,
Autophagy & Lysosomes ⓘ
autolysosome↑, 1, Beclin-1↓, 1, Beclin-1↑, 2, LC3‑Ⅱ/LC3‑Ⅰ↓, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 2, LC3II↓, 1, LC3s↑, 2, p62↓, 2, p62↑, 1, p‑p62↑, 1, TumAuto↑, 7,
DNA Damage & Repair ⓘ
ATR↑, 1, DNAdam↑, 10, GADD45A↑, 1, P53↑, 6, p‑P53↑, 2, PARP↓, 1, PARP↑, 2, cl‑PARP↑, 3, PCNA↓, 1, γH2AX↑, 1, p‑γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 4, CDK4↓, 4, cycA1/CCNA1↓, 1, CycB/CCNB1↓, 1, cycD1/CCND1↓, 3, cycE/CCNE↓, 2, P21↑, 5, TumCCA↑, 14,
Proliferation, Differentiation & Cell State ⓘ
cFos↓, 1, CSCs↓, 1, EIF4E↓, 1, EMT↓, 4, EMT↝, 1, p‑ERK↑, 1, FGF↓, 1, FGFR2↓, 1, FOXO↓, 1, p‑GSK‐3β↓, 1, HDAC↓, 2, IGFR↓, 1, mTOR↓, 4, p‑mTOR↓, 1, mTORC1↓, 1, Nanog↓, 1, OCT4↓, 1, PI3K↓, 3, PTEN↑, 2, STAT1↓, 1, STAT3↓, 4, p‑STAT3↓, 1, TCF-4↓, 1, TOP1↓, 2, TOP2↓, 1, TumCG↓, 7, tyrosinase↓, 1, Wnt↓, 1,
Migration ⓘ
AP-1↓, 2, Ca+2↓, 1, Ca+2↑, 8, E-cadherin↓, 1, E-cadherin↑, 2, MMP2↓, 2, MMP7↓, 1, MMP9↓, 4, N-cadherin↓, 1, PDGF↓, 1, Slug↓, 1, Snail↓, 1, TGF-β↓, 1, TIMP1↑, 1, TumCA↑, 1, TumCI↓, 4, TumCMig↓, 5, TumCP↓, 8, TumMeta↓, 3, Twist↓, 1, uPA↓, 1, Vim↓, 2, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 4, ATF4↑, 1, EGFR↓, 2, EPR↑, 1, Hif1a↓, 6, Hif1a↑, 1, NO↑, 1, PDGFR-BB↑, 1, VEGF↓, 3, VEGFR2↓, 1,
Barriers & Transport ⓘ
BBB↑, 1, CellMemb↑, 1, GLUT1↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 3, CXCR4↓, 1, HCAR2↑, 1, IL6↓, 1, Imm↑, 2, Imm↝, 1, Inflam↓, 1, NF-kB↓, 4, NF-kB↑, 2, NK cell↑, 1, PD-L1↑, 1, PGE2↓, 1, TNF-α↓, 1, TNF-α↑, 1,
Cellular Microenvironment ⓘ
cGAS–STING↑, 1,
Protein Aggregation ⓘ
NLRP3↓, 1,
Hormonal & Nuclear Receptors ⓘ
CDK6↓, 4,
Drug Metabolism & Resistance ⓘ
BioAv↑, 2, BioEnh↑, 1, ChemoSen↑, 9, Dose↝, 3, Dose∅, 1, eff↓, 5, eff↑, 11, RadioS↑, 5, selectivity↑, 13,
Clinical Biomarkers ⓘ
ALAT↓, 1, AST↓, 1, EGFR↓, 2, GutMicro↑, 1, HER2/EBBR2↓, 1, hTERT/TERT↓, 1, IL6↓, 1, LDH↓, 3, PD-L1↑, 1,
Functional Outcomes ⓘ
AntiCan↑, 2, AntiTum↑, 1, CardioT↑, 1, chemoP↑, 1, chemoPv↑, 2, hepatoP↓, 1, neuroP↑, 1, OS↑, 2, toxicity↑, 1, toxicity↝, 1, TumVol↓, 1, Weight↑, 1,
Infection & Microbiome ⓘ
CD8+↑, 1,
Total Targets: 248
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 4, Catalase↑, 1, GPx↑, 1, GSH↑, 2, HO-1↑, 2, MDA↓, 2, MPO↓, 1, NRF2↑, 5, ROS↓, 4, ROS↝, 1, SOD↑, 3, TBARS↓, 1,
Mitochondria & Bioenergetics ⓘ
mtDam↑, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 1, glucose↓, 1, LDH↓, 1, PPARα↝, 1,
Cell Death ⓘ
Casp↓, 1, iNOS↓, 1, JNK↓, 1,
Protein Folding & ER Stress ⓘ
ER Stress↓, 1, HSP70/HSPA5↑, 1,
Migration ⓘ
Ca+2↓, 1, TGF-β↓, 1, TRPC1↓, 1,
Angiogenesis & Vasculature ⓘ
p‑eNOS↑, 1, Hif1a↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, IL10↑, 2, IL17↓, 1, IL6↓, 2, Inflam↓, 5, NF-kB↓, 2, TLR4↓, 1, TNF-α↓, 3,
Synaptic & Neurotransmission ⓘ
AChE↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Hormonal & Nuclear Receptors ⓘ
RAAS↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, Dose↓, 1, eff↑, 1,
Clinical Biomarkers ⓘ
BP↓, 1, IL6↓, 2, LDH↓, 1,
Functional Outcomes ⓘ
AntiDiabetic↑, 1, AntiTum↑, 1, cardioP↑, 2, cognitive↑, 1, hepatoP↑, 1, memory↑, 2, neuroP↑, 4, Obesity↓, 1, toxicity↓, 1,
Total Targets: 53
Scientific Paper Hit Count for: mtDam, mitochondrial damage
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#:614 State#:% Dir#:2
wNotes=on sortOrder:rid,rpid
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