MitoP Cancer Research Results
MitoP, Mitophagy: Click to Expand ⟱
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Mitophagy—the selective autophagic removal of damaged mitochondria—is now regarded as a core upstream process in Alzheimer’s disease pathophysiology, not a secondary epiphenomenon. Impairment of mitophagy precedes overt amyloid and tau pathology and helps explain early synaptic failure and neuronal vulnerability.
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Scientific Papers found: Click to Expand⟱
*cardioP↑, Review of the pharmacological effects of astragaloside IV and its autophagic mechanism in association with inflammation - PMC
*MitoP↑, The mechanism included promotion of mitophagy, which reduced generation of mitochondrial ROS and accumulation of damaged mitochondria[31].
*ROS↓, AS-IV can reduce ROS-mediated autophagosome accumulation and myocardial injury caused by I/R[21]
*mtDam↓,
*neuroP↓, Ischemic stroke MCAO in SD rats; OGD/R in HT22 cells A neuroprotective role (-) apoptosis (+) autophagy
TumAuto↓, For NSCLC cells treated with cisplatin, AS-IV inhibited the increased autophagy of proteins Beclin1 and LC3 I/II
*AntiDiabetic↑, Protective effect of AS-IV on diabetes
TRPV2↑, Mechanistically, calcium flux induced by CBD through TRPV4 (transient receptor potential cation channel subfamily V member 4) activation played a key role in mitophagy initiation
Ca+2↑,
MitoP↑,
eff↑, Lastly, CBD and temozolomide combination therapy in patient-derived neurosphere cultures and mouse orthotopic models showed significant synergistic effect
*MitoP↑, DOPAC promotes mitophagy by preventing KEAP1-mediated degradation of NRF2
*NRF2↑, Mechanistically, DOPAC directly binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), disrupting its interaction with nuclear factor erythroid 2-related factor 2 (NRF2) and preventing KEAP1-mediated degradation of NRF2 in CD8+ T cells.
eff↑, DOPAC synergizes with immune checkpoint blockade to suppress tumor growth.
*eff↓, In this study, we found that eliminating gut microbiota with antibiotics disrupted the anti-tumor effect of dietary quercetin.
*GutMicro↑, these findings highlight the role of gut microbiota in utilizing dietary quercetin to counteract tumors, suggesting gut microbe-derived DOPAC as a promising candidate for cancer therapy and a potential amplifier of ICB therapy.
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
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U87MG |
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T98G |
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A172 |
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TumAuto↑, selenite induces autophagy in which mitochondria serve as the main target.
ROS↑, high levels of superoxide anion were generated
TumCD↑, Sodium selenite induces nonapoptotic cell death in human glioma cells
tumCV↓, 1 to 7 μmol/L selenite decreased viability in the tested glioma cell lines
selectivity↑, suggesting that selenite is preferentially cytotoxic to malignant glioma cells over normal astrocytes.
MMP↓, selenite induced a significant loss of MMP beginning 4 h after treatment
eff↓, Moreover, selenite-induced AVO formation was almost completely inhibited by CuDIPS, MnTBAP, or NAC but not by PEG-catalase
MitoP↑, Collectively, these results show that selenite induces excessive mitophagy.
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AD, |
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Park, |
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Stroke, |
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*MitoP↑, key biological effects of UA, including its promotion of mitophagy and mitochondrial homeostasis, as well as its anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties
*Inflam↓,
*antiOx↑,
*Risk↓, UA’s therapeutic potential in CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, and stroke.
*Aβ↓, UA enhances microglial phagocytosis of Aβ plaques, suppresses neuroinflammation, and reduces tau hyperphosphorylation by restoring mitophagy to eliminate abnormal mitochondria
*p‑tau↓,
*p62↓, In doxorubicin-induced cardiomyopathy mice, UA upregulates p62, LC3-II, PINK1, and Parkin expression, restoring impaired mitophagy, mitigating membrane potential loss and ROS accumulation,
*PARK2↑,
*MMP↑,
*ROS↓,
*Strength↑, Randomized controlled trials in healthy middle-aged and older adults show that oral supplementation with 500–1000 mg of UA significantly improves skeletal muscle endurance and mitochondrial efficiency, reduces plasma inflammatory markers (such as C-r
*CRP↓,
*IL1β↓, UA activates sirtuin 1 (SIRT1)-mediated deacetylation of NF-κB p65, suppressing glial cell activation and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α)
*IL6↓,
*TNF-α↓,
*AMPK↑, UA enhances brain adenosine 5′-monophosphate-activated protein kinase (AMPK) activation, attenuating NF-κB and MAPK activity, mitigating neuroinflammation, and supporting synaptic recovery
*NF-kB↓,
*MAPK↓,
*p62↑, In a renal ischemia-reperfusion injury model, UA activates the p62—kelch-like ECH-associated protein 1 (Keap1)—nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, boosting superoxide dismutase and catalase activity while lowering ROS levels
*NRF2↑,
*SOD↑,
*Catalase↑,
*HO-1↑, UA upregulates the Keap1-Nrf2/heme oxygenase 1 (HO-1) pathway to inhibit ferroptosis and reduce lipid peroxide accumulation in lung tissue
*Ferroptosis↓,
*lipid-P↓,
*Cartilage↑, reducing cartilage degradation and synovial inflammation
*PI3K↓, UA suppresses the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and Akt/IκB kinase (IKK)/NF-κB signaling pathways, reducing neuronal apoptosis while enhancing BBB integrity and neurological outcomes
*Akt↓,
*mTOR↓,
*Apoptosis↓,
*neuroP↑,
*Bcl-2↓, cerebral artery occlusion model, UA treatment lowers Bcl-2 expression and elevates Bcl-2 associated X protein (Bax) and caspase-3 levels
*BAX↑,
*Casp3↑,
*ATP↑, UA restores mitochondrial membrane potential and ATP production in cardiomyocytes, balancing carnitine palmitoyltransferase1-dependent fatty acid oxidation to reduce apoptosis
*eff↑, in humanized homozygous amyloid beta knockin mice modeling late-onset AD, UA combined with green tea extract (Epigallocatechin gallate) more effectively reduces brain Aβ40 and Aβ42 levels compared to UA alone [106].
*motorD↑, UA administration elevated striatal dopamine levels and enhanced motor coordination, accompanied by suppression of NLRP3 inflammasome activation
*NLRP3↓,
*radioP↑, In a radiation-induced primary astrocyte model, UA activated the PINK1/Parkin-mediated mitophagy pathway, significantly reducing ROS levels in both cells and mitochondria,
*BBB↑, preclinical studies showing that UA primarily crosses the mouse BBB
*memory↑, Long-term UA treatment significantly improved learning, memory and olfactory function in different AD transgenic mice.
*Aβ↓, UA also reduced Aβ and Tau pathologies, and improved long-term potentiation
*tau↓,
*MitoP↑, UA activated autophagy/mitophagy via increasing lysosomal functions
*lysosome↑,
*CTSZ↝, UA improved lysosomal function and normalized lysosomal cathepsins, especially targeting cathepsin Z, to restore lysosomal function in AD
*neuroP↑, urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy.
*Half-Life↝, Urolithins appear in the human circulation within a few hours of consumption of ET-containing foods, reaching maximum concentrations after 24–48 h and complete excretion in urine/faeces within 72 h.
*BBB↑, urolithins can permeate the blood–brain barrier (BBB)
*toxicity↓, Urolithins are relatively non-toxic, as shown by studies in rats. The lethal dose 50 (LD50) has been found to be greater than 5 g/kg body weight in rat
*Inflam↓, In a study of Fisher rats [185], urolithin A was found to be the most effective anti-inflammatory compound derived from pomegranate consumption.
*Strength↑, Another clinical trial has shown that UA at doses of 500 mg and 1,000 mg for 4 weeks modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elders [
*BACE↓, There is evidence suggesting that these molecules inhibit BACE1 activity, leading to reduced Aβ production.
*Aβ↓,
*MitoP↑, Urolithin A May Trigger Mitophagy
*SIRT1↑, Activation of SIRT1/3, AMPK, PGC1-α and Inhibition of mTOR1
*SIRT3↑,
*AMPK↑,
*PGC-1α↑,
*mTOR↓,
*PARK2↑, urolithin A (1000 mg) has been shown to transcriptionally increase Parkin and BECN1 levels after 28 days of treatment in humans
*Beclin-1↑,
*ROS↓, by their actions to reduce BACE1 activity, Aβ fibrillation, ROS damage, inflammation
*GutMicro↑, impact on the microbiome may be an additional contribution to reducing AD risk
*Risk↓,
*motorD↑, increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory
*memory↑,
*MitoP↑, mitophagy and autophagy genes were upregulated
*Aβ↓, The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment
*mitResp↑, Mitochondrial respiration is stronger for urolithin A compared to EGCG, indicating that mitophagy enhancer, urolithin A is a better and more promising molecule to enhance mitophagy activity.
*Nrf1↑, table4
*PINK1↑,
*PARK2↑,
*ATG5↑,
*Bcl-2↑,
*H2O2↓, we found hydrogen peroxide levels were reduced in urolithin A (p = 0.0008) and urolithin A+EGCG (p = 0.0004) treated hAbKI mice relative to untreated mice.
*ROS↓, urolithin A and EGCG act as free radical scavengers in hAbKI mice
*lipid-P↓, (lipid peroxidation) were also significantly reduced in urolithin A (p = 0.0003) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to untreated hAbKI mice
*mt-ATP↑, mitochondrial ATP levels were increased in urolithin A (p = 0.007) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to hAbKI untreated mice.
*cognitive↑, t has been reported that ET- or EA-rich food consumption improve cognition and memory in the elderly (summarized in Table 3), whereas the effect of Uros supplementation in the elderly is still unknown.
*memory↑,
*antiOx↑, aUros are potent antioxidants with good BBB permeability
*BBB↑,
*ROS↓, they effectively inhibited ROS formation and lipid peroxidation
*lipid-P↓,
*Catalase↑, UroA and UroB increased the activity of antioxidant enzymes, including catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase
*SOD↑,
*GSR↑,
*GPx↑,
*CREB↑, we found that UroA (5, 10 μM) treatment significantly increased protein kinase A (PKA)/cAMP-response element binding protein (CREB)/brain derived neurotrophic factor (BDNF) neurotrophic signaling pathway in H2O2-treated SH-SY5Y cells,
*BDNF↑,
*neuroP↑, CREB/BDNF neurotrophic signaling pathway might involve the neuroprotective effect of UroA against oxidative stress.
*Inflam↓, Mitigation of Neuroinflammatioin
*MitoP↑, Promotion of Mitophagy and Mitochondrial Function
*Aβ↓, inhibition of Aβ and tau pathology
*tau↓,
*NLRP3↓, UroA reduced the elevated expression and activity of NLRP3 and related neuroinflammation in AD mice
*SIRT1↑, UroA activates SIRT1 and SIRT3
*SIRT3↑,
Showing Research Papers: 1 to 10 of 10
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
lipid-P↑, 1, ROS↑, 2,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 1, MMP↓, 2,
Cell Death ⓘ
lysoMP↑, 1, MOMP↑, 1, necrosis↑, 1, TumCD↑, 1,
Kinase & Signal Transduction ⓘ
TRPV2↑, 1,
Transcription & Epigenetics ⓘ
tumCV↓, 1,
Protein Folding & ER Stress ⓘ
ER Stress↑, 1, UPR↑, 1,
Autophagy & Lysosomes ⓘ
autoF↓, 1, lysosome↝, 1, MitoP↑, 3, TumAuto↓, 1, TumAuto↑, 1,
DNA Damage & Repair ⓘ
DNAdam↑, 1,
Proliferation, Differentiation & Cell State ⓘ
CSCs↓, 1,
Migration ⓘ
Ca+2↑, 2,
Drug Metabolism & Resistance ⓘ
eff↓, 1, eff↑, 2, selectivity↑, 1,
Total Targets: 24
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 2, Catalase↑, 2, Ferroptosis↓, 1, GPx↑, 1, GSR↑, 1, H2O2↓, 1, HO-1↑, 1, lipid-P↓, 3, Nrf1↑, 1, NRF2↑, 2, PARK2↑, 3, ROS↓, 5, SIRT3↑, 2, SOD↑, 2,
Mitochondria & Bioenergetics ⓘ
ATP↑, 1, mt-ATP↑, 1, mitResp↑, 1, MMP↑, 1, mtDam↓, 1, PGC-1α↑, 1, PINK1↑, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 2, CREB↑, 1, SIRT1↑, 2,
Cell Death ⓘ
Akt↓, 1, Apoptosis↓, 1, BAX↑, 1, Bcl-2↓, 1, Bcl-2↑, 1, Casp3↑, 1, Ferroptosis↓, 1, MAPK↓, 1,
Autophagy & Lysosomes ⓘ
ATG5↑, 1, Beclin-1↑, 1, lysosome↑, 1, MitoP↑, 7, p62↓, 1, p62↑, 1,
Proliferation, Differentiation & Cell State ⓘ
mTOR↓, 2, PI3K↓, 1,
Migration ⓘ
Cartilage↑, 1,
Barriers & Transport ⓘ
BBB↑, 3,
Immune & Inflammatory Signaling ⓘ
CRP↓, 1, CTSZ↝, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 3, NF-kB↓, 1, TNF-α↓, 1,
Synaptic & Neurotransmission ⓘ
BDNF↑, 1, tau↓, 2, p‑tau↓, 1,
Protein Aggregation ⓘ
Aβ↓, 5, BACE↓, 1, NLRP3↓, 2,
Drug Metabolism & Resistance ⓘ
eff↓, 1, eff↑, 1, Half-Life↝, 1,
Clinical Biomarkers ⓘ
CRP↓, 1, GutMicro↑, 2, IL6↓, 1,
Functional Outcomes ⓘ
AntiDiabetic↑, 1, cardioP↑, 1, cognitive↑, 1, memory↑, 3, motorD↑, 2, neuroP↓, 1, neuroP↑, 3, radioP↑, 1, Risk↓, 2, Strength↑, 2, toxicity↓, 1,
Total Targets: 72
Scientific Paper Hit Count for: MitoP, Mitophagy
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
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