HMGCR Cancer Research Results

HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR): Click to Expand ⟱
Source:
Type:
3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)
– HMGCR catalyzes the conversion of HMG-CoA to mevalonate, a critical step in the cholesterol biosynthesis pathway.
– Cholesterol is essential for maintaining cell membrane integrity and serves as a precursor for steroid hormones, which can influence tumor growth.

– In certain contexts, elevated HMGCR expression has been linked to more aggressive tumor phenotypes, increased proliferation, and, in some cases, poorer overall survival.
Scientific Papers found: Click to Expand⟱
1544- Api,    The flavone apigenin blocks nuclear translocation of sterol regulatory element-binding protein-2 in the hepatic cells WRL-68
- in-vitro, Nor, WRL68
*SREBF2↓, apigenin prevented SREBP-2 translocation and reduced the downstream gene HMGCR transcription
*HMGCR↓,
*Dose∅, oral dosages of 5.4 mg apigenin/kg body weight would produce a C max value of 16.5 μm in serum
*BioAv?, Given its high bioavailability, its action on cholesterol synthesis could be achievable in this administrative method

5454- ATV,    Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility
- Review, BC, NA
HMG-CoA↓, Statins, inhibitors of mevalonate metabolic pathway
HMGCR↓, Statins are specific inhibitors of the 3-hydroxy-methylglutaryl CoA reductase (HMGCR)
TumCP↓, statins have recently been found to also have multiple anticancer effects such as antiproliferative, proapoptotic, antiinvasive, and radiosensitizing properties
RadioS↑,
CD44↓, n breast cancer, statins prevented metastasis by inhibiting CD44 expression through promoting p53 expression (25)
P53↑,

5451- ATV,    In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells
- in-vitro, BC, MDA-MB-231 - in-vitro, GBM, U87MG - in-vitro, GBM, A172
TumAuto↑, cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines.
CSCs↓,
HMG-CoA↓, These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells.
TumCP↓, Statins inhibit proliferation/viability of human tumour cell lines
tumCV↓,
TumCCA↑, Statins induce cell cycle arrest in tumour cells
TumCG↓, Statins inhibit tumour growth in animal models
HMGCR↓, Statins are competitive inhibitors of HMGCR, which converts HMG-CoA to mevalonate.

5448- ATV,    Beyond cardiovascular health: The pharmacotherapeutic potential of statins in oncology
- Review, Var, NA
Apoptosis↑, Despite statins’ ability to induce apoptosis or autophagy, arrest cell cycle, or modulate favorable epigenetic reprogramming, their efficacy is highly context-dependent
TumAuto↑,
TumCCA↑,
BioAv↓, Challenges such as statin resistance, low bioavailability and pharmacokinetic variability further complicate their application in oncology.
eff↑, including nanoparticle-based drug delivery systems and combination therapies with chemotherapy, radiotherapy or immunotherapy, appear to help overcome these limitations.
HMGCR↓, statins reduce cholesterol levels by targeting HMGCR
LDL↓,
cardioP↑, statins have become a cornerstone in the management of hypercholesterolemia and the prevention of cardiovascular diseases [23], [24], [25], [26].
AntiTum↑, Notably, while research suggests that statins possess anti-tumor effects, evidence remains conflicting and highly context-dependent
ChemoSen↑, suggest that statins can sensitize cancer cells to chemotherapy and radiotherapy, potentially improving treatment outcomes,
RadioS↑,
toxicity↓, Statins are widely regarded as safe and well-tolerated. However, like any medication, they are not without potential side effects, though these are generally mild [232].

5449- ATV,    Pleiotropic effects of statins: A focus on cancer
- NA, Var, NA
lipid-P↓, Statins exhibit “pleiotropic” properties that are independent of their lipid-lowering effects.
TumCG↓, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types.
Apoptosis↑,
ChemoSen↑, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling.
RAS↓,
HMG-CoA↓, Statins are potent, competitive inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR).
HMGCR↓,
LDL↓, Statins reduce blood plasma cholesterol levels by decreasing de novo cholesterol biosynthesis and by inducing changes in low density lipoprotein (LDL) receptor expression [2].
toxicity↓, Due to the well-established safety profile of statins, such studies are less expensive than the development of novel drugs.
Risk↓, statin use in cancer patients was associated with reduced cancer-related mortality. The risk of cancer death was significantly lower in postmenopausal women
P21↑, Other proposed mechanisms leading to an increase of p21 levels include the release of promoter-associated histone deacetylase and inhibition of histone deacetylase
HDAC↓,
Bcl-2↓, Statins trigger the intrinsic apoptosis pathway and decrease Bcl-2 protein expression [[154], [155], [156]], increase Bax and BIM protein expression [[156], [157], [158], [159]], and activate several caspases
BAX↑,
BIM↑,
Casp↑,
cl‑PARP↑, thereby increasing cleaved PARP-1 levels.
MMP↓, different tumor cell lines (breast, brain, and lung) showed that simvastatin-induced apoptosis is dependent on decreasing mitochondrial membrane potential and increasing reactive oxygen species (ROS) production
ROS↑,
angioG↓, Statins inhibit angiogenesis and metastasis
TumMeta↓,
PTEN↑, n breast cancer xenografts, simvastatin prevented tumor growth by reducing Akt phosphorylation and BclXL transcription, while simultaneously increasing the transcription of pro-apoptotic/anti-proliferative PTEN
eff↑, In mice, the administration of a combination of celecoxib and atorvastatin was more effective than each individual treatment, and effectively prevented prostate cancer progression from androgen dependent to androgen independent
OS↑, Long-term statin use may improve survival in GBM patients treated with temozolomide chemotherapy
Remission↑, statin use during or after chemotherapy is not associated with improved disease-free-, recurrence-free-, or overall survival in stage II colon cancer patients

4988- ATV,  Dipy,    Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin–Dipyridamole Combination Treatment in Melanoma Cell Lines
- in-vivo, Melanoma, NA
HMGCR↓, Metastatic melanoma has a very poor prognosis. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, are cholesterol-lowering agents with a potential for cancer treatment.
SREBP2↑, The inhibition of HMGCR by statins, however, induces feedback, which paradoxically upregulates HMGCR expression via sterol regulatory element-binding protein-2 (SREBP2)
SREBP2↓, Dipyridamole, an antiplatelet agent, is known to inhibit SREBP2 upregulation.
AntiAg↑,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

lipid-P↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

HMG-CoA↓, 3,   LDL↓, 2,   SREBP2↓, 1,   SREBP2↑, 1,  

Cell Death ⓘ

Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   Casp↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 2,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 1,   CSCs↓, 1,   HDAC↓, 1,   HMGCR↓, 5,   PTEN↑, 1,   RAS↓, 1,   TumCG↓, 2,  

Migration ⓘ

AntiAg↑, 1,   TumCP↓, 2,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 2,   eff↑, 2,   RadioS↑, 2,  

Functional Outcomes ⓘ

AntiTum↑, 1,   cardioP↑, 1,   OS↑, 1,   Remission↑, 1,   Risk↓, 1,   toxicity↓, 2,  
Total Targets: 39

Pathway results for Effect on Normal Cells:


Core Metabolism/Glycolysis ⓘ

SREBF2↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

HMGCR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv?, 1,   Dose∅, 1,  
Total Targets: 4

Scientific Paper Hit Count for: HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)
5 Atorvastatin
1 Apigenin (mainly Parsley)
1 Dipyridamole
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#:1133  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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