PARK2 Cancer Research Results

PARK2, PARKIN: Click to Expand ⟱

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PARKIN (also known as PARK2) is an E3 ubiquitin ligase that plays a crucial role in mitochondrial quality control, cell cycle regulation, and apoptosis. Although PARKIN is best known for its involvement in Parkinson’s disease, an increasing number of studies have investigated its role in cancer.
-PARKIN is recruited to damaged mitochondria, which are often sources of elevated ROS due to impaired electron transport chains.
-By targeting dysfunctional mitochondria for autophagic degradation (mitophagy), PARKIN helps to mitigate excessive ROS production, preserving cellular redox balance.

-Reduced PARKIN expression generally correlates with more aggressive disease and worse prognosis in various cancers, including breast, lung, colorectal, liver, and pancreatic cancers.

Scientific Papers found: Click to Expand⟱

2047-

Buty,

Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells

in-vitro,

CRC,

T24/HTB-9

0-10mM

in-vitro,

Nor,

SV-HUC-1

in-vitro,

Bladder,

5637

in-vivo,

NA,

200 mg/kg/day, i.g., n = 5

mice

HDAC↓, Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells
AntiTum↑,
TumCMig↓, NaB inhibited migration
AMPK↑, induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis
mTOR↑,
TumAuto↑,
ROS↑, NaB initiates ROS overproduction
miR-139-5p↑, NaB upregulates miR-139-5p and depletes Bmi-1 in bladder cancer cells
BMI1↓,
TumCI?, NaB significantly inhibited cell migration dose-dependently
E-cadherin↑, E-cadherin was markedly increased, while the expression of N-cadherin, Vimentin, and Snail was decreased
N-cadherin↓,
Vim↓,
Snail↓,
cl‑PARP↑, increased expression levels of cleaved PARP, cleaved caspase-3, and Bax and the concurrent decrease in Bcl-2 and Bcl-xl
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
MMP↓, impairs mitochondrial membrane potential
PINK1↑, activates the PINK1/ PARKIN pathway
PARK2↑,
TumMeta↓, NaB inhibits tumor metastasis and growth in vivo
TumCG↓,
LC3II↑, a significant increase in the levels of cleaved caspase3, p-AMPK, and LC3B-II along with decreased Bmi-1 and Vimentin
p62↓, elevated LC3B-II levels and degradation of p62
eff↓, NAC abolished the impairment of MMP and ROS overproduction. Interestingly, NAC also significantly inhibited apoptosis induced by NaB

2863-

HNK,

Honokiol induces paraptosis-like cell death through mitochondrial ROS-dependent endoplasmic reticulum stress in hepatocellular carcinoma Hep3B cells

in-vitro,

Liver,

Hep3B

ER Stress↑, Honokiol also enhanced ER stress, increased cellular calcium ion (Ca2+) levels, and caused mitochondrial dysfunction
Ca+2↑,
mtDam↑,
PTEN↑, Honokiol upregulated the expression of mitophagy regulators such as PTEN-induced kinase 1 and Parkin in the mitochondria
PARK2↑,
Alix/AIP‑1↓, whereas the expression of apoptosis-linked gene 2-interacting protein X (Alix), involved in suppressing paraptosis, was downregulated.
ROS↑, honokiol-induced cytotoxicity was accompanied by excessive generation of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS).
mt-ROS↑,

4869-

Uro,

Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges

Review,

AD,

Review,

Park,

Review,

Stroke,

*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

4864-

Uro,

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease

Review,

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↓,

4862-

Uro,

Neuroprotective effect of Urolithin A via downregulating VDAC1-mediated autophagy in Alzheimer's disease

in-vivo,

AD,

mice

in-vitro,

Nor,

PC12

*cognitive↑, UA improved cognitive dysfunction and reduced Aβ deposition in APP/PS1 mice
*p‑PI3K↓, UA down-regulated the phosphorylation level of PI3K/AKT/mTOR and up-regulated the phosphorylation level of AMPK
*p‑Akt↓,
*AMPK↑,
*VDAC1↓, UA down-regulated VDAC1
*neuroP↑, These findings demonstrated that UA down-regulated VDAC1 played a key neuroprotective role on AD by inhibiting the PI3K/AKT/mTOR pathway and activating the AMPK pathway to promote autophagy.
*PARK2↑, Mechanistically, UA may increase the expression of Parkin (Parkinson’s disease related-1) and PINK1 (PTEN induced kinase 1), and the LC3BII/I
*PTEN↑,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p62↓, by inhibiting VDAC1, and reduce the expression level of p62, activating autophagy.
*Aβ↓, UA treatment significantly decreased the number of Aβ plaques in the hippocampus of APP/PS1 mice compared with APP/PS1 mice
*Apoptosis↓, UA inhibits Aβ-induced apoptosis and promotes autophagy

4874-

Uro,

EGCG,

A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer's Disease

in-vivo,

AD,

humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer’s disease

*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.

4875-

Uro,

Impact of the Natural Compound Urolithin A on Health, Disease, and Aging

Review,

AD,

Review,

Stroke,

Review,

ostP,

Review,

IBD,

*MitoP↓, Experimental models consistently show that UA increases mitophagy and mitochondrial function and blunts excessive inflammatory responses.
*Strength↑, UA is a promising strategy to target health and disease conditions of aging, especially those linked to mitochondrial and muscle dysfunction.
*PINK1↑, UA can activate. PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy starts with the stabilization of the kinase PINK1,
*PARK2↑, which recruits and phosphorylates the ubiquitin-conjugating protein Parkin.
*Inflam↓, anti-inflammatory effect of UA was reported for the first time as a decrease in mRNA and protein levels of the inflammatory marker cyclooxygenase 2 (COX2)
*COX2↓,
*IL1β↓, In neuronal tissues, UA treatment reduced levels of IL-1β, IL-6, and TNFα in the brains of the amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD
*IL6↓,
*TNF-α↓,
*OS↑, impact on worm longevity showed that UA extends lifespan by 45%,
*cardioP↑, reduction in IRI markers, such as circulating creatine kinase and lactate dehydrogenase levels, and by fewer apoptotic cells in the heart
*memory↑, Increased learning, memory retention, neuronal survival, and neurogenesis in the hippocampus was achieved with UA administration in the APP/PS1 mouse model of AD
*neuroG↑,
*neuroP↑, UA was shown to have neuroprotective effects in the EAE mouse model of multiple sclerosis (MS)
*Cartilage↑, In a model of osteoarthritis, an age-related and disabling joint disease caused by a slow degeneration of cartilage,
*Inflam↓, UA has protective effects against a chronic DSS-induced model of IBD, leading to reduced levels of colon inflammation markers and to better mucosal integrity.
*RenoP↑, UA consistently reduced tubular damage induced by cisplatin, as shown by histopathology and by a reduction in circulating markers of kidney damage
*eff↑, When administered as nanoparticles to increase its bioavailability, UA even improved the survival of mice that received a lethal dose of cisplatin
*Dose↝, UA showed a favorable safety profile, with no observed side effects following either single oral administration of UA up to 2000 mg or multiple oral dosing (28 days) of UA up to 1000 mg daily.
*Half-Life↑, It showed a relatively long-half life (t1/2 = 17–22 hours),
*NRF2↑, Other mechanisms of action have been proposed for UA, such as the activation of the Ahr/Nrf2 pathway and its downstream antioxidative stress response
*GutMicro↑, A recent report also showed an impact of direct UA supplementation on gut microflora in obese rats

2274-

VitK2,

Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop

in-vitro,

Nor,

SH-SY5Y

(0–40 µM) for 6 h

SH-SY5Y cells are similar to neurones and are a widely used neurodegenerative diseases model

*Bcl-2↓, Vitamin K2 played a significant part in apoptosis by upregulating and downregulating Bcl-2 and Bax protein expressions, respectively, which inhibited mitochondrial depolarization, and ROS accumulation to maintain mitochondrial structure and function
*BAX↑,
*MMP↑, vitamin K2 can restore the mitochondrial membrane potential and inhibit mitochondrial depolarization caused by 6-OHDA.
*ROS↓, vitamin K2 can effectively remove the ROS generated by 6-OHDA and relieve cellular oxidative stress.
*p62↓, vitamin K2 treatments downregulated the expression level of p62 and upregulated the expression level of LC3A
*LC3A↑,
*Dose↝, vitamin K2 inhibited the toxic effect of 6-OHDA, and that the inhibitory effect was the best at a concentration of 30 µM
*Apoptosis↓, However, after vitamin K2 post-treatment, the apoptosis rate was significantly reduced to 11.44%.
*PINK1↑, Vitamin K2 Regulates Mitochondrial Quality-Control System by Activating Pink1/Parkin Signaling Pathway
*PARK2↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

AntiTum↑, 1,
Total Targets: 33

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Catalase↑, 1, Ferroptosis↓, 1, H2O2↓, 1, HO-1↑, 1, lipid-P↓, 2, Nrf1↑, 1, NRF2↑, 2, PARK2↑, 6, ROS↓, 4, SIRT3↑, 1, SOD↑, 1, VDAC1↓, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1, mt-ATP↑, 1, mitResp↑, 1, MMP↑, 2, PGC-1α↑, 1, PINK1↑, 3,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 3, SIRT1↑, 1,

Cell Death ⓘ

Akt↓, 1, p‑Akt↓, 1, Apoptosis↓, 3, BAX↑, 2, Bcl-2↓, 2, Bcl-2↑, 1, Casp3↑, 1, Ferroptosis↓, 1, MAPK↓, 1,

Autophagy & Lysosomes ⓘ

ATG5↑, 1, Beclin-1↑, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, LC3A↑, 1, MitoP↓, 1, MitoP↑, 3, p62↓, 3, p62↑, 1,

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 2, neuroG↑, 1, PI3K↓, 1, p‑PI3K↓, 1, PTEN↑, 1,

Migration ⓘ

Cartilage↑, 2,

Barriers & Transport ⓘ

BBB↑, 2,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, CRP↓, 1, IL1β↓, 2, IL6↓, 2, Inflam↓, 4, NF-kB↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 4, BACE↓, 1, NLRP3↓, 1,

Drug Metabolism & Resistance ⓘ

Dose↝, 2, eff↑, 2, Half-Life↑, 1, Half-Life↝, 1,

Clinical Biomarkers ⓘ

CRP↓, 1, GutMicro↑, 2, IL6↓, 2,

Functional Outcomes ⓘ

cardioP↑, 1, cognitive↑, 1, memory↑, 2, motorD↑, 2, neuroP↑, 4, OS↑, 1, radioP↑, 1, RenoP↑, 1, Risk↓, 2, Strength↑, 3, toxicity↓, 1,
Total Targets: 74

Scientific Paper Hit Count for: PARK2, PARKIN

5 Urolithin
1 Butyrate
1 Honokiol
1 EGCG (Epigallocatechin Gallate)
1 Vitamin K2

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#:1240  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

PARK2 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Autophagy & Lysosomes ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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