MOMP Cancer Research Results

MOMP, Mitochondrial Outer Membrane Permeabilization: Click to Expand ⟱
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Type:
MOMP is the point-of-no-return decision step of intrinsic apoptosis. It is the event in which the mitochondrial outer membrane becomes permeable, allowing release of pro-death factors that irreversibly commit a cell to die. Cancer progression is characterized by systematic suppression, buffering, or decoupling of MOMP from lethal execution.

MOMP occurs when BAX and/or BAK oligomerize in the mitochondrial outer membrane, forming pores that release:
-Cytochrome c → apoptosome → caspase-9
-Smac/DIABLO → IAP neutralization
-Other apoptogenic factors (e.g., Omi/HtrA2)
Once sufficient mitochondria undergo MOMP, cell death is inevitable (even if caspases are later inhibited).
Redox, Metabolism, and MOMP (Critical)
-High xCT / GSH → suppress mitochondrial ROS → MOMP ↓
-Autophagic flux → removes damaged mitochondria → MOMP ↓
-Pro-oxidant overload → mitochondrial dysfunction → MOMP ↑


Scientific Papers found: Click to Expand⟱
5378- ART/DHA,    Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives
- Review, Var, NA
Ferroptosis↑, Artemisinin increases ferroptosis risk in cancer cells by increasing cellular free iron and lipid peroxidation, causing increased membrane permeability and decreased integrity [59]
Iron↑,
lipid-P↑,
MOMP↑,
AntiCan↑, Artemisinin has anticancer and antimalarial properties by upregulating NCOA4 and DMT1 levels, raising ferrous ion levels, and causing ferroptosis by downregulating GSH and GPX4 levels [30, 59, 75].
NCOA4↑,
GSH↓,
GPx4↓,
ROS↑, Artemisinin and its derivatives regulate 20 iron metabolism genes, thereby causing the formation of ROS [76]
ChemoSen↑, Artesunate, when combined with sorafenib, can enhance the susceptibility of hepatocellular carcinoma cells to cisplatin resistance through ferroptosis inhibition [77].
ER Stress↑, artemisinin, specifically ferroptosis, by controlling iron metabolism, producing ROS, and triggering ER‐stress.
DNAdam↑, primary antineoplastic mechanisms of artemisinin are ferroptosis, DNA damage, tumour angiogenesis suppression and cell cycle inhibition [78]
angioG↓,
TumCCA↑,
eff↓, while NAC and ferrostatin‐1 partially reverse these effects [82]

5130- ART/DHA,    Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway
- in-vitro, Bladder, T24/HTB-9
tumCV↓, DHA significantly reduced cell viability in a dose-dependent manner.
eff↓, Cytotoxicity of DHA was suppressed by N-acetylcysteine (NAC)
Apoptosis↑, induction of cell apoptosis, which were manifested by annexin V-FITC staining, activation of caspase-3
Casp3↑,
ROS↑, DHA also increased ROS generation, cytochrome c release, and loss of mitochondrial transmembrane potential (ΔΨm) in cells.
Cyt‑c↑,
MMP↓,
Bcl-2↓, downregulation of regulatory protein Bcl-2 and upregulation of Bax protein by DHA were also observed
BAX↑,
MOMP↑, Dihydroartemisinin increases mitochondrial permeability of EJ-138 and HTB-9 cells by Collapse of ΔΨm
TumCG↓, It has shown that DHA selectively inhibits the growth of many cancer cells types, such as leukemia,[29] pancreas,[30] breast[31] and prostate[32] cancers

6350- DRE,    Tracking Evidences of Dandelion for the Treatment of Cancer: From Chemical Composition, Bioactivity, Signaling Pathways in Cancer Cells to Perspective Study
- Review, Var, NA
AntiCan↑, Dandelion, one of the important medicinal and edible plants, is effective in anticancer, inhibition of bacterial growth, hypoglycemic, and anti-inflammation, as well as antioxidant.
*Bacteria↓,
*Inflam↓,
*antiOx↑,
TumCCA↑, Cell Cycle Arrest and Anti-Proliferation in Cancer Cells
Apoptosis↑, Induction of Cell Apoptosis in Cancer Cells
MOMP↑, increased permeability of the outer mitochondrial membrane and mediating the release of cytochrome c (Cyt-c).
Cyt‑c↑,
APAF1↑, activating factor-1 (Apaf-1) and cystein asparate protease-9 (Caspase-9)
Casp9↑,
Casp3↑, then activates Caspase-3 to trigger the Caspase cascade reaction and induce cell apoptosis.
MMP↓, disrupting mitochondrial membrane potential, activating Caspase-9 and Caspase-3, and downregulating the expression of Bcl-2 in human breast cancer MDA-MB-231
Bcl-2↓,
TumCMig↓, Inhibition of Migration and Invasion of Cancer Cells
TumCI↓,
Wnt↓, taraxasterol inhibits the migration and invasion of human thyroid papillary carcinoma TPC-1 and BCPAP cells by regulating Wnt/β-catenin signaling and suppressing the expression of MMP-2 and MMP-9
β-catenin/ZEB1↓,
MMP2↓,
MMP9↓,
TumAuto↑, Induction of Autophagy in Cancer Cells
mTOR↓, inhibiting the mTOR/ eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) pathway.
4E-BP1↓,
Glycolysis↓, Taraxasterol significantly reduces the level of glyceraldehyde-3-phosphate dehydrogenase in aerobic glycolysis,
angioG↓, Anti-Angiogenesis in Cancer Cells

6367- DRE,    Antioxidant and antimicrobial activities of Dandelion root extract (Taraxacum officinale) and its cytotoxic effect on MDA-MB-231 breast cancer cells
- in-vitro, BC, MDA-MB-231
TumCD↑, Our study indicates that DRE has proven novel in killing breast cancer cells, has a mildly vigorous antioxidant activity to scavenge free radicals,
*antiOx↑,
*ROS↓,
tumCV↓, fig 3
Apoptosis↑, dandelion root can cause apoptosis in MDA-MB-231 cells, that DRE has antioxidant properties against reactive oxygen species
ROS↑, The degradation of the breast cancer cells might be due to the presence of ROS groups and the action of some bioactive compounds like polyphenols and triterpenoids in the extract.
TumCCA↑, DRE through G2/M cell cycle arrest and alteration in the amino acids (Figs. 5, 6) that make up the endoplasmic reticulum
MOMP↑, The DRE penetrates the outer membrane, causing ROS to disrupt the mitochondria, breakage of the double strand in the DNA
ROS↑,

6836- EMD,    Emodin and the Anthraquinone Scaffold: Therapeutic Promise and Strategies to Overcome Translational Barriers
- Review, Nor, NA
*antiOx↑, graphic abstract
*neuroP↑,
*Inflam↓,
*hepatoP↑,
AntiTum↑,
*Bacteria↓,
*diuretic↑,
*AntiDiabetic↑,
*BioAv↝, formulation composition and herb–herb or herb–drug interactions are critical determinants of anthraquinone bioavailability and, ultimately, therapeutic outcomes.
*NF-kB↓, figure 4
*AMPK↑,
*JAK↓,
*STAT3↓,
*ROS↓, At low to moderate concentrations, particularly in models of inflammatory or oxidative tissue injury, emodin exerts net antioxidant and cytoprotective effects by lowering ROS levels, limiting lipid peroxidation, and enhancing endogenous antioxidant d
*lipid-P↓,
ROS↑, in cancer cells and other metabolically stressed conditions, the anthraquinone scaffold has been reported to act predominantly as a pro-oxidant, shifting redox homeostasis toward oxidative stress and promoting intracellular ROS accumulation,
TumCCA↑, In human colon cancer (WiDr) cells, aloe-emodin induced a pronounced G2/M arrest associated with suppression of cyclin B1, a critical regulator of mitotic entry.
CycB/CCNB1↓,
BAX↑, upregulation of Bax and Bak alongside the downregulation of anti-apoptotic members such as Bcl-2 and Bcl-xL.
Bcl-2↓,
MOMP↑, As a result, mitochondrial outer-membrane permeabilization (MOMP) is promoted, enabling cytochrome c release and subsequent apoptosome formation through association with Apaf-1.
Cyt‑c↑,
Casp9↑, Activation of initiator caspase-9 follows, triggering executioner caspases, notably caspase-3 and caspase-7, and culminating in apoptotic cell death
Casp3↑,
Casp7↑,
Apoptosis↑,
P53↑, where emodin-induced ROS accumulation and p53 activation contribute to the inhibition of pathological proliferation relevant to restenosis and atherosclerotic remodeling

5519- EP,    Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions
- Review, Var, NA
MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

7250- Gink,    Ginkgetin from Ginkgo biloba: mechanistic insights into anticancer efficacy
- Review, Var, NA
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

7321- Gos,    The potential roles of gossypol as anticancer agent: advances and future directions
- Review, Var, NA
other↝, Except in China, where gossypol is available on the drug market as an adjuvant used for tumour treatment [85], in the rest of the world, gossypol is still under clinical trials investigation.
BioAv↑, To improve the water solubility and bioavailability of gossypol, Wang et al. [76] used gossypol-loaded pluronic F127 nanoparticles (GLPFNs), which increased bioavailability several times and exhibited higher organ uptake of the drug compared to using
Bcl-2↓, The main mechanism of gossypol-anticancer activity is inducing apoptosis through suppressing anti-apoptotic proteins of the Bcl-2 family.
Casp3↑, The caspase-dependent anti-tumour effect of gossypol is led by activation of caspase-3 and caspase-9.
Casp9↑,
MOMP↑, Apoptosis induced by independent pathways is made by alternations on the mitochondrial outer membrane permeabilisation
ROS↑, Gossypol treatment has been demonstrated to induce the production of reactive oxygen species (ROS) in tumour cell
ATP↓, 80 μmol/L gossypol resulted in a significant increase in cellular ROS levels, leading to ATP depletion, which induces mitochondrial dysfunction
mtDam↑,
Apoptosis↑, The impaired function of mitochondria further contributes to the activation of apoptosis
hTERT/TERT↓, ↓ decrease, telomerase reverse transcriptase (TERT)
Akt↓, ↓ decrease, telomerase reverse transcriptase (TERT), Adenosine triphosphate (ATP), Cellular myelocytomatosis oncogene (c-MyC), serine/threonine protein kinase (Akt)
TumAuto↑, Induction of autophagy as a complementary process of apoptosis
LC3‑Ⅱ/LC3‑Ⅰ↑, gossypol in colorectal cancer cells increased the LC3-II/LC3-I ratio and induced autophagy
NRF2↓, gossypol reduced Nrf2 protein stability, leading to the inhibition of the Nrf2/ARE pathway, resulting in a significant decrease of cell viability in human cancer cells
ARE↓,
ICAM-1↓, Treating breast cancer cells with gossypol has been shown to block the binding of NF-κB to the promoter regions of ICAM-1, suppressing TNF-α-induced ICAM-1 expression.
CX43/GJA1↓, It down-regulates the expression of CX43, nuclear NF-κB, TNF-α, toll-like receptor 4 (TLR4), and interleukin-6 (IL-6) in these cells, indicating its potential anti-inflammatory and anti-apoptotic effects
NF-kB↓,
TLR4↓,
IL6↓,
Inflam↓,
CUL5↝, gossypol has been found to block the neddylation of cullin enzymes (CUL5 and CUL1) by directly binding to the SAG-CUL5 or RBX1-CUL1 complex.
CUL1↝,
NOXA↑, This leads to the accumulation of both the pro-apoptotic protein NOXA
TumCI↓, gossypol significantly reduced the invasion, migration, and adhesion of these cancer cells by suppressing the FAK pathway and ETM
TumCMig↓,
TumCA↓,
FAK↓,
MDM2↓, gossypol, the binding between the MDM2 protein and VEGF mRNA was disrupted in breast cancer cells [78]. As a result, the expression of MDM2 and VEGF proteins is significantly decreased.
VEGF↓,
angioG↓, anti-angiogenic mechanism of gossypol in cancer cells (Fig. 7).
HLA-I/II↑, gossypol has been found to increase the expression of HLA-I/II molecules
Imm↑, This immune modulation may contribute to its anti-cancer activity by enhancing immune recognition and response against tumour cells
Dose↝, phase III clinical trial performed between January 2014 and February 2017, gossypol acetate tablets (20 mg/tablet) produced by Xi’an Northern Pharmaceutical Co., Ltd were tested with a placebo in 102 patients with NSCLC
Glycolysis↓, Moreover, the treatment of boars with gossypol inhibited glycolysis and the respiratory chain, leading to a decrease in oxidative phosphorylation and adenosine triphosphate (ATP) synthesis, causing a decrease in energy supply and inhibition of sperm
OXPHOS↓,

7311- Gos,    Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials
- Review, CLL, NA
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↑,

7310- Gos,    Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells
- in-vitro, AML, NA
TumCD↑, Gossypol induced cell death in a concentration- and time-dependent manner; 24-hour incubation with 30 μM gossypol resulted in 50% cell death
MOMP↑, Starting at 4 hours, the mitochondrial outer membrane was significantly permeabilized
ROS↑, Mitochondrial outer membrane permeabiliztaion (MOMP) was concurrent with increased production of reactive oxygen species (ROS);
ATP↓, Mitochondrial membrane permeabilization was also associated with loss of intracellular adenosine triphosphate (ATP), activation of BAX, and release of cytochrome c and apoptosis-inducing factor (AIF), which was translocated to the nucleus.
BAX↑,
Cyt‑c↑,
AIF↑,

7335- Gra,    Effect of Annona muricata (Soursop) on Patients with Cancer: A Systematic Review
- Review, Var, NA
TumCG↓, Annona muricata has shown to inhibit cancer cell growth, enhance caspase activity, and provide anti-inflammatory effects.
Casp↑,
Inflam↓,
toxicity↓, It was found to be safe, with minimal side effects in cancer patients. Annona muricata does not interfere with bone marrow, liver, and kidney function and may even improve nutritional status
other↑, Annona muricata is among the most commonly used herbal remedies by cancer patients.
TumCCA↑, by inducing tumour cell death via various mechanisms such as controlling the cell cycles (causing cell arrest in the G1 phase), and promoting apoptosis by inhibiting multiple proteins while also inducing autophagy
Apoptosis↑,
TumAuto↑,
ATP↓, acetogenins can inhibit mitochondrial ATP formation and suppress cancer cell growth by facilitating the nuclear translocation of apoptosis-inducing factor (AIF) and promoting AIF-dependent cell death
AIF↑,
MMP↓, cascade of caspases. Annomuricin E causes a reduction in mitochondrial membrane potential (MMP), which results in the opening of mitochondrial permeability transition pores and the subsequently release of pro-apoptotic proteins like cytochrome C.
MOMP↑,
Cyt‑c↑,
selectivity↑, One mouse study reported that Annona muricata significantly inhibited the growth of MDA-MB-468 cell lines, with an IC50 of 4.8 μg/ml, while showing no effect on MCF-10 cell lines
hepatoP∅, owing that Annona muricata did not induce hepatotoxicity and nephrotoxicity.

6487- Nimb,    Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development
- Review, Var, NA
TumCP↓, anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes.
Apoptosis↓,
TumMeta↑,
angioG↓,
*antiOx↑, nimbolidehas been found to possess antioxidant effect and free radical scavenging activities.
*eff↑, In comparison to azadirachtin and ascorbic acid (vitamin C), nimbolide was shown to be a more potent antioxidant
Apoptosis↑, Nimbolide induces apoptosis through diverse molecular mechanism(s).
MOMP↑, Nimbolide disrupts MOMP, which promotes caspases activation leading to apoptosis.
CDK1↓, Nimbolide also reduces the level of CDKs and cyclins, causing cell cycle arrest.
TumCCA↑,
MAPK↓, Nimbolide also abrogates various signaling cascades including MAPK (ERK1/2), JAK2/STAT3 and PI3K/Akt, leading to suppression of proliferation of a wide variety of human cancer cells.
JAK2↓,
STAT3↓,
PI3K↓,
Akt↓,
TumCP↓,
*NRF2↑, Nimbolide disrupts the Nrf2-KEAP1 complex and promotes the release of Nrf2, thus increasing levels of antioxidant and detoxification enzymes.
NF-kB↓, Inhibition of the NF-κB pathway also reduces the dissociation of GSK-3β from β-catenin, hence restraining the Wnt/β-catenin
GSK‐3β↑,
Wnt↓,
β-catenin/ZEB1↓,
chemoPv↑, nimbolide showed remarkable chemopreventive property.
Bcl-xL↓, Nimbolide treatmentdecreased the expression of antiapoptotic proteins(Bcl-xL, Bcl-2, survivin, caspase inhibitor molecules) and increased the expression of proapoptotic proteins (cytochrome c, Bax, Bad, Bid, cleaved caspases) in prostate cancer cells
Bcl-2↓,
survivin↓,
Cyt‑c↑,
BAX↑,
BID↑,
cl‑Casp↑,
P53↑, nimbolide acted by up-regulation of p53 levelin HeLa cells, thereby priming these cells towards apoptosis by destabilizing the mitochondria
DR5↑, Nimbolide up-regulated the expression of both DR5 and DR4 in chronic myeloid leukemia (KBM-5), multiple myeloma (U266), embryonic kidney carcinoma (A293), pancreatic adenocarcinoma (AsPC-1), and breast adenocarcinoma (MDA-MB-231) cells
DR4↑,
ROS↑, nimbolide resulted in generation of reactive oxygen species (ROS)
lipid-P↑, ROS also induced lipid peroxidation of cellular membranes, generating toxic metabolites such as malondialdehyde (MDA) that can react with DNA to form adducts to induce apoptosis.
MDA↑,
MMP2↓, nimbolide reduced mRNA expression of MMP-2, MMP-9, uPA and uPA receptor in breast cancer cells (MCF-7)
MMP9↓,
uPA↓,
ICAM-1↓, nimbolide was shown to downregulate the expression of MMP-9, ICAM-1, and CXCR4 in colorectal cancer xenografts
CXCR4↓,
CXCR2↓, nimbolide also reduced expression of CXCL8 and CXCR2 in breast cancers, and thus abrogated angiogenesis
angioG↓,
BBB↑, nimbolide might be able to cross blood-brain barrier (BBB) and the concentration could be sufficient for nimbolide to suppress intracranial tumour cell proliferation.

5125- Sal,    Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma
- in-vitro, GBM, NA
ER Stress↑, SLM induces a potent endoplasmic reticulum (ER) stress followed by the trigger of the unfolded protein response (UPR) and an aberrant autophagic flux that culminated in necrosis due to mitochondria and lysosomal alterations.
UPR↑,
autoF↓, SLM treatment does not trigger apoptosis and blocks the autophagy flux in glioma cell line
lysosome↝,
ROS↑, aberrant autophagic flux was orchestrated by the production of Reactive Oxygen Species (ROS)
lipid-P↑, our data suggest that in our system the oxidative stress blocks the autophagic flux through lipid oxidation.
CSCs↓, SLM induces a potent antitumor effect in brain tumor stem cells (BTSCs) and established adult and pediatric glioma cell lines in vitro
necrosis↑, SLM induces necrosis cell death
ATP↓, with increasing doses of SLM displayed a decrease in intracellular ATP levels
MMP↓, SLM treated cells displayed significantly lower ΔΨm than untreated cells
MOMP↑, SLM induces mitochondrial MOMP.
DNAdam↑, We observed double strand breaks in SLM-treated cells (Figure 4C) and it is possible that this DNA damage is induced as a consequence of AIF internalization.
AIF↑,
lysoMP↑, hypothesis that SLM treatment triggers an autophagic process that cannot proceed adequately because of LMP resulting from oxidative stress.
MitoP↑, In addition, impairment of mitochondrial activity would trigger mitophagy, with engulfment of the organelle and initiation of autophagy.
Ca+2↑, The elevated levels of calcium and ROS inside mitochondria results in MOMP


Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

APE1/APEX1↓, 1,   CUL1↝, 1,   CUL5↝, 1,   CX43/GJA1↓, 1,   HLA-I/II↑, 1,   PFS↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ARE↓, 1,   Ferroptosis↑, 2,   GPx4↓, 2,   GSH↓, 1,   HO-1↓, 1,   Iron↑, 1,   lipid-P↑, 3,   MDA↑, 1,   NRF2↓, 2,   OXPHOS↓, 1,   ROS↑, 12,   xCT/SLC7A11↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

NCOA4↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 3,   ATP↓, 4,   ETC↝, 1,   MMP↓, 5,   MMP↑, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↑, 1,   CYP3A4↓, 1,   Glycolysis↓, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   APAF1↑, 1,   Apoptosis↓, 1,   Apoptosis↑, 8,   BAX↑, 4,   Bcl-2↓, 6,   Bcl-xL↓, 1,   BID↑, 1,   Casp↑, 2,   cl‑Casp↑, 1,   Casp3↑, 6,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp9↑, 6,   cl‑Casp9↑, 1,   Cyt‑c↑, 8,   DR4↑, 1,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↑, 2,   hTERT/TERT↓, 1,   lysoMP↑, 1,   MAPK↓, 1,   MDM2↓, 1,   MOMP↑, 13,   necrosis↑, 1,   NOXA↑, 1,   survivin↓, 1,   TumCD↑, 4,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,   other↝, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 3,   HSP90↓, 1,   UPR↑, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

autoF↓, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   lysosome↝, 1,   MitoP↑, 1,   TumAuto↑, 4,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 3,   P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CycB/CCNB1↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

4E-BP1↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 2,   GSK‐3β↑, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 2,   Wnt↓, 2,  

Migration(tgid=13) ⓘ

Ca+2↑, 2,   FAK↓, 1,   MMP2↓, 2,   MMP9↓, 2,   TumCA↓, 1,   TumCI↓, 3,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↑, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 6,   EPR↑, 1,   VEGF↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CXCR2↓, 1,   CXCR4↓, 1,   HMGB1↓, 1,   ICAM-1↓, 2,   IL6↓, 1,   Imm↑, 3,   Inflam↓, 2,   JAK2↓, 1,   NF-kB↓, 2,   TLR4↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 4,   Dose↓, 1,   Dose↑, 2,   Dose↝, 6,   eff↓, 2,   eff↑, 3,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↑, 1,   AST↑, 1,   hTERT/TERT↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3,   AntiTum↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   hepatoP∅, 1,   OS↑, 1,   toxicity↓, 3,   toxicity↑, 1,  
Total Targets: 132

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

diuretic↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 4,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   SIRT1↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

STAT3↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2,   JAK↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1,   eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   AntiDiabetic↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   toxicity↑, 1,   toxicity↝, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 2,  
Total Targets: 21

Scientific Paper Hit Count for: MOMP, Mitochondrial Outer Membrane Permeabilization
3 Gossypol/AT-101
2 Artemisinin
2 Dandelion Root
1 Emodin
1 Electrical Pulses
1 Ginkgetin
1 Graviola
1 Nimbolide
1 salinomycin
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#:1434  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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