HMG-CoA Cancer Research Results

HMG-CoA, Mevalonate pathway: Click to Expand ⟱

Source:

Type:

HMG‐CoA (3‐hydroxy-3‐methylglutaryl‐coenzyme A)

Mevalonate pathway → Primary pathway entry
-HMG-CoA reductase (HMGCR) → rate-limiting node / druggable target
-Downstream nodes: prenylation, cholesterol synthesis, CoQ

HMG‐CoA is not a single enzyme but rather a key metabolic intermediate in the mevalonate pathway that underlies cholesterol and isoprenoid biosynthesis.
– HMG‐CoA is a pivotal intermediate formed from acetyl‐CoA (via the enzyme HMG‐CoA synthase) that subsequently undergoes reduction (via HMG‐CoA reductase) to produce mevalonate.
– The mevalonate pathway supplies cholesterol and other isoprenoids, which are essential for membrane biogenesis, protein prenylation, and other cellular functions that support cell proliferation and survival.
– The availability of HMG‐CoA and subsequent metabolites has implications for modifying cell signaling pathways, including those involved in the regulation of cell growth, differentiation, and apoptosis.
– Markers of an activated mevalonate pathway (such as increased expression of HMG‐CoA synthase or HMG‐CoA reductase) have been associated with aggressive tumor phenotypes in several cancer types, including breast, prostate, and liver cancers.

Scientific Papers found: Click to Expand⟱

5454-

ATV,

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Review,

BC,

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↑,

5452-

ATV,

Mevalonate pathway in pancreatic ductal adenocarcinoma: mechanisms driving metabolic and cellular plasticity

Review,

Var,

ChemoSen↑, The study further highlighted that statins, which inhibit the mevalonate pathway, could significantly reduce protein glycosylation and enhance chemotherapy sensitivity by suppressing EMT signatures in PDAC organoid models.
HMG-CoA↓,
EMT↓,
Ferroptosis↑, cancer cells upregulate the mevalonate pathway to manage oxidative stress and evade ferroptosis and that inhibiting this pathway, either by statins or fatostatin, an SREBP1 inhibitor, can trigger ferroptotic death.
Hif1a↓, pharmacological inhibition of the mevalonate pathway using statins reduces HIF-1α levels

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.

5447-

ATV,

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

Review,

Var,

Risk↓, increasing amount of data, from preclinical and epidemiological studies, that support an inverse association between the use of statins, potent inhibitors of MVA biosynthetic pathway, and mortality rate in specific cancers
Dose↑, cancer treatment demands the use of relatively high doses of single statins for a prolonged period, thereby limiting this therapeutic strategy due to adverse effects.
ChemoSen↑, synergistic effects of tolerable doses of statins with conventional chemotherapy might enhance efficacy with lower doses of each drug and, probably, reduce adverse effects and resistance.
chemoP↑,
HMG-CoA↓, potential use of MVA pathway inhibitors to improve therapeutic window in cancer.
EMT↓, statins may suppress epithelial-mesenchymal transition (EMT) program together with the inhibition of cancer stem cell generation, maintenance, and expansion
CSCs↓,
HH↝, inhibitors of MVA pathway (e.g., statins) that modulate Hh pathway activity could represent potential drugs in Hh pathway-related cancers.
YAP/TEAD↝, MVA participates in the regulation of YAP-TAZ expression and transcriptional activity and reveal an original process through which statins have anticancer effects.

5446-

ATV,

Targeting the Mevalonate Pathway in Cancer

Review,

Var,

EMT↓, In a phase II clinical trial of atorvastatin in breast cancer, RhoB, a tumor suppressing Rho family member, was increased and promoted the reversion of EMT, demonstrating that EMT can be targeted in the clinic [47,48].
HMG-CoA↓, first and foremost class of mevalonate pathway inhibitors: statins [4].

5445-

ATV,

Atorvastatin

NA,

Nor,

*cardioP↑, atorvastatin is FDA-approved for the prevention of cardiovascular events in patients with cardiac risk factors and abnormal lipid profiles.[1]
*LDL↓, patients should be prescribed high-intensity statin therapy to achieve a ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) and reduce the risk of major adverse cardiovascular events (MACE).
HMG-CoA↓, Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.[12]
Half-Life↝, Atorvastatin is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The half-life of atorvastatin is about 14 hours, while its active metabolites have a half-life of about 20 to 30 hours.
BioAv↓, The bioavailability is low at 14% due to extensive first-pass metabolism.
Dose↝, Atorvastatin is available as atorvastatin calcium tablets in strengths of 10, 20, 40, and 80 mg. It is also available as an oral suspension in a strength of 20 mg/5 mL.[20]

5449-

ATV,

Pleiotropic effects of statins: A focus on cancer

NA,

Var,

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

4982-

ATV,

Inhibiting the mevalonate pathway with atorvastatin alters gut microbiota and has potential as an anti-cancer treatment for ovarian cancer

in-vivo,

Ovarian,

Female C57BL/6 mice

HMG-CoA↓, Statins, a mevalonate (MVA) pathway antagonist, are widely used to treat and prevent hypercholesterolemia by blocking cellular production of cholesterol.
GutMicro↑, Furthermore, statins have been shown to induce significant changes in intestinal enterotypes in both humans and mice. statins favorably alter the intestinal microbiome

4981-

ATV,

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

Apoptosis↑, The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity.
selectivity↑,
eff↑, Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.
HMG-CoA↓, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, are a commonly used and well-tolerated class of drugs used in lipid disorders,
*cardioP↑, Their effectiveness in preventing the development of cardiovascular diseases makes statins one of the most widely used drugs
OS↑, On the other hand, improved survival in patients with hepatocellular carcinoma, colon cancer or prostate cancer is visible after the use of any statin
IL1β↓, statins inhibit the synthesis of cytokines, including interleukin (IL-) IL-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α)
IL6↓,
IL8↓,
TNF-α↓,
TumAuto↑, Simvastatin-induced autophagy has been reported in rhabdomyosarcoma cells [
Histones↝, Statins are also involved in the regulation of the histone acetylation level.
ac‑H3↑, Studies indicate that statins increase histone H3 and H4 acetylation as well as inhibit class I and II HDACs
ac‑H4↑,
HDAC↓,

4980-

ATV,

A review of effects of atorvastatin in cancer therapy

Review,

Var,

HMG-CoA↓, atorvastatin as a reductase (HMG-CoA) inhibitor might affect proliferation, migration, and survival of cancer cells.
TumCP↓,
TumCMig↓,

4985-

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,

SK-MEL-28

in-vitro,

BC,

MDA-MB-435

HMG-CoA↓, 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.
eff↑, the inexpensive and frequently prescribed statin–dipyridamole combination therapy may lead to new developments in the treatment of melanoma and may potentiate the effects of vemurafenib for the targeted therapy of BRAF V600E-mutation bearing melanoma
HMGCR⇅, Atorvastatin Upregulates HMGCR mRNA Expression in a Dose-Dependent Manner While Dipyridamole Tends to Downregulate It
ChemoSen↑, combining conventional chemo- and/or targeted therapies with new drugs to improve therapeutic outcomes

4986-

ATV,

Dipy,

The combination of statins and dipyridamole is effective preclinically in AML, MM, and breast cancer

Review,

Var,

HMG-CoA↓, Statins are drugs that have been utilized for years to treat hyperlipidemia through inhibition of the rate-limiting enzyme of the mevalonate (MVA) pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)
AntiAg↑, Dipyridamole (DP), a commonly prescribed anti-platelet agent potentiated the anti-cancer effects of atorvastatin
eff↑, DP-statin combination was synergistic and capable of inducing apoptosis in a variety of acute myelogenous leukemia (AML), MM and breast cancer cell lines.
Apoptosis↑, DP-statin combination also induced apoptosis in primary AML patient samples, but was not toxic to normal PBSCs.
selectivity↑,
*toxicity↓,
TumCG↓, In an in vivo AML tumor model, the DP-statin combination was found to be effective at inhibiting tumor growth.
PDE4↓, DP is known to elicit numerous effects, amongst them, phosphodiesterase (PDE) inhibition
other↑, . As both statins and DP are pre-approved for use in humans, off-patent, and readily available, they have the potential to directly impact patient care.

6022-

CGA,

Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome

Review,

Nor,

*antiOx↑, including anti-oxidant, anti-inflammatory, antilipidemic, antidiabetic, and antihypertensive activities.
*Inflam↓,
*AntiDiabetic↑,
*Obesity↓, chlorogenic acid as a nutraceutical for the prevention and treatment of metabolic syndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms of action
*Wound Healing↑, It was found that chlorogenic acid accelerated wound healing.
*BP↓, Significant reductions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed
*Dose↝, A total of 23 healthy subjects (four men and 19 women) were given water (control) and 400 mg of chlorogenic acid dissolved in 200 mL of low nitrate water.
*ROS↓, the mechanism proposed was that chlorogenic acid scavenges reactive oxygen species (ROS) generated by consumption of high-fat diet, which suppresses the expression of inflammation, and consequently reduces fat accumulation,
*Fas↓, chlorogenic acid supplementation in high-fat diet-induced-obese mice significantly inhibited fatty acid synthase (FAS),
*HMG-CoA↓, As for hypercholesterolemia, chlorogenic acid has been found to inhibit 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR)
*GutMicro↑, high-CGAs coffee (80.8 mg) induced a significant increase in the growth of Bifidobacterium spp. as well as Clostridium coccoides-Eubacterium rectale group, the latter group having also potential to benefit human health.

6010-

CGA,

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

Review,

Nor,

*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

6683-

DCA,

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Review,

Var,

PDK1↓, classic DCA target, pyruvate dehydrogenase kinase
lactateProd↓, reduce lactic acid production which would push the cell towards oxidative phosphorylation: this would be the supposed function of dichloroacetate (DCA).
Apoptosis↑, They found that DCA induced apoptosis and decreased proliferation by restoring mitochondrial oxidative metabolism, without toxicity to normal cells.
TumCP↓,
selectivity↑,
other↝, many clinics, usually called “DCA Clinics” have opened, mainly in Canada and Germany.
Dose↝, DCA is sold over the counter and is produced by many laboratories. The quality of the product from these laboratories is not well established. These particulars explain many of the doubts about DCA’s real value as a therapeutic tool.
BioAv↑, DCA is an orally available molecule that is quickly and almost completely absorbed by the digestive system
Half-Life↓, With a 10 mg/kg infusion the maximum plasma concentration achieved was between 19.9 μg/ml and 24.7 μg/ml with a half life of only 20 minutes. If the infused dose was increased to 20 mg/kg the plasma concentration was between 57.3 and 74.9 μg/ml with
Glycolysis↓, facilitates the switch from a glycolytic to an oxidative metabolism.
OXPHOS↑,
Casp↑, onversion to an oxidative metabolism by DCA, is an increase in caspase-mediated apoptosis
i-pH↓, pHi decreases (at least temporarily).
COX2↑, DCA increases the expression of COX2 and the latter increases tumor resistance to DCA. Therefore, a possible integrated treatment could be COX2 inhibitor co-administered with DCA
Hif1a↓, DCA suppresses HIF-1α activity and angiogenesis through the inhibition of PDK-II
angioG↓,
HMG-CoA↓, figure 7
GSTZ1↓,
OCR↑,
lipoGen↓,
fatigue↓,
survivin↓, Survivin (an inhibitor of apoptosis) expression was decreased and miR-375 (a microRNA which acts as a tumor suppressor) levels were increased.
miR-375↑,
eff↓, African Americans are known to respond poorly to therapy compared with Caucasian American patients.
CSCs↓, DCA can inhibit the cancer stem cell like characteristics of the cells and strongly influenced the metabolic pathway of the cells causing a shift from glycolysis to oxidative phosphorylation.
TumAuto↑, DCA induced autophagy in human colon cancer cells with ROS production and mTOR inhibition,
mTOR↓,
TumCI↓, DCA induced apoptosis, inhibited invasion, and angiogenesis. In mouse experiments in vivo with the melanoma allografts, DCA reduced volume and weight of tumors.
TumVol↓,
TumW↓,
ATP↓, DCA alone reduced glycolytic activity and intracellular ATP levels and inhibited cellular growth in melanoma cells.
Warburg↓, DCA was also found to interrupt the Warburg effect and decreased proliferation.
eff↑, The co-application of metformin and DCA suppressed human liver cancer cell proliferation inducing apoptosis through inhibition of mTORC1 and increased ROS in vitro and in vivo
e-pH↑, when measuring extracellular pH in vivo found that an initial increase in extracellular pH of tumors in mice when treated with DCA.
eff↑, To avoid the development of this type of metabolic resistance DCA should be given simultaneously with other metabolic drugs such as metformin [327] or 2 deoxyglucose.
eff↑, chronic co-administration of DCA with sodium bicarbonate to tumor bearing mice prolonged survival
other↝, High doses of thiamin (vit B1) have effects similar to those of DCA: reduced PDH phosphorylation, reduced lactate prod and increased casp3 activity with reduced proliferation in colon cancer cells. can vitB1 replace DCA as a nontoxic PDK inhibitor?
RadioS↑, Dong et al. [380] found that DCA radiosensitized esophageal carcinoma cells in vitro and in vivo through increased ROS accumulation.
toxicity↓, 25 mg/Kg/day may show a mild sedative effect or drowsiness. The most serious published side effect is reversible peripheral neuropathy
Dose↝, 10 to 50 mg/kg body weight/day has been found to be a safe dose. However, single nucleotide polymorphisms (SNPs) in the gene of the enzyme GSTZ1 cause difficulties in establishing a universal dose [409] as noted above.
eff↑, There is strong evidence showing that the association of metformin and DCA has significant cytotoxic effects.
eff↑, To this approach we must add a third compound: a COX2 inhibitor like celecoxib to decrease COX2 expression induced by DCA.
eff↑, the triple association of DCA, metformin and celecoxib, which has never been experimentally tested in patients, deserves well planned phase II clinical trials.
toxicity↝, DCA will never become a stand-alone chemotherapeutic compound. The fundamental reason for this statement is that the drug can only reach micromolar blood concentrations without toxicity and requires millimolar levels to be cytotoxic.
eff↓, DCA should not be used in association with allopurinol, NSAIDs, or flavonoids because they reduce cellular DCA uptake.

4984-

Dipy,

ATV,

Immediate Utility of Two Approved Agents to Target Both the Metabolic Mevalonate Pathway and Its Restorative Feedback Loop

in-vitro,

AML,

eff↑, The statin–dipyridamole combination was synergistic and induced apoptosis in multiple myeloma and AML cell lines and primary patient samples, whereas normal peripheral blood mononuclear cells were not affected.
Apoptosis↑,
selectivity↑,
TumCG↓, This novel combination also decreased tumor growth in vivo.
HMG-CoA↓, Statins block HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the MVA pathway.
HMGCR↑, Dipyridamole blunted the feedback response, which upregulates HMGCR and HMG-CoA synthase 1 (HMGCS1) following statin treatment.

4983-

Dipy,

ATV,

Targeting tumor cell metabolism via the mevalonate pathway: Two hits are better than one

Review,

Var,

HMG-CoA↓, Statins are promising anticancer agents that target the mevalonate pathway
AntiTum↓, dipyridamole inhibits this feedback response and potentiates statin antitumor activity.
eff↑, this combination of 2 FDA-approved drugs has the potential to be fast-tracked to cancer patient care.

6730-

Dipy,

ASA,

Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner

vitro+vivo,

CRC,

CRC mouse models, i.e. an orthotopic xenograft mouse model,

*AntiThr↑, dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes.
eff↑, We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone.
ER Stress↑, induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect.
UPR↑,
*AntiAg↑,
*COX1↓, aspirin acts through inhibiting cyclooxygenase-1 (COX-1) in platelets.
Risk↓, Combined use of dipyridamole and aspirin associates with a low risk of CRC through a nationwide population-based cohort study
TumCG↓, The combination of dipyridamole with aspirin has an enhanced inhibitory effect on tumor growth in orthotopic CRC mouse model and AOM/DSS-induced CRC mouse model
Apoptosis↑, The combination of dipyridamole with aspirin inhibits CRC cell growth and promotes CRC cell apoptosis
HMG-CoA↓, Dipyridamole can also suppress the activity of SREBF2, a transcription factor regulating the expression of HMGCS1 to compromise the mevalonate (MVA) signaling pathway in inhibiting colon cancer
*Inflam↓, Dipyridamole has anti-inflammatory [40, 41] and anti-oxidant [42, 43] functions.
*antiOx↓,

6564-

Ger,

Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

in-vitro,

HCC,

HepG2

TumCG↓, Up to 100 micromol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells.
HMG-CoA↓,
TumCP↓, Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation.
eff↑, n particular, geraniol inhibits HMG-CoA reductase activity in human liver (Elson and Yu 1994) and cell lines (Duncan et al. 2004)
Dose↝, The concentrations used were comparable to those reported in blood for similar isoprenoids in human pharmacokinetic studies (Ripple et al. 1998, 2000).

6568-

Ger,

Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells

in-vitro,

Colon,

Caco-2

HMG-CoA↓, Since geraniol is a well known inhibitor of mevalonate metabolism
MMP↓, Geraniol (400 microM) induced membrane depolarization with a decrease of membrane resistance due to local perforation of the cell membrane.
PKCδ↓, Incubation of Caco-2 cells with geraniol (400 microM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity.
ERK↓, After 16 h of incubation, geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK).

1575-

statins,

Citrate,

Inhibition of Lung Cancer Growth: ATP Citrate Lyase Knockdown and Statin Treatment Leads to Dual Blockade of Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol-3-Kinase (PI3K)/AKT Pathways

in-vitro,

NSCLC,

A549

Generation of ACL knockdown cell lines

eff↑, we find that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which act downstream of ACL in the cholesterol synthesis pathway, dramatically enhance the anti-tumor effects of ACL inhibition, even regressing tumors
HMG-CoA↓, statins, inhibitors of (HMG-CoA) reductase
eff↑, statins dramatically enhance the anti-tumor effects of ACL inhibition
AntiTum↑,
EGFR↓, reduce the growth of EGF receptor
eff↑, ACL knockdown cells, H2O2 induced more apoptosis, which was further amplified with statin treatment (Fig. 1I). These data suggest that oxidant stress can tip ACL knockdown cells into apoptosis and that statin treatment magnifies this effect.
ROS↑, suggesting involvement of reactive oxygen species (ROS) in the induction of apoptosis by PI3K inhibitors.
EMT↓, Reversal of EMT
E-cadherin↑, increase in E-cadherin
MUC1↑, Mucin staining in ACL knockdown tumors is markedly increased, further suggesting that differentiation is induced in this condition
p‑ACLY↓, Statin treatment downregulates the phosphorylation of ACL and AKT
p‑Akt↓,
eff↑, . In A549 cells, Na-citrate supplementation caused a slight downregulation of AKT phosphorylation

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 2, Catalase↑, 1, GPx↑, 1, GSH↑, 1, HDL↑, 1, HO-1↓, 1, Keap1↓, 1, MDA↓, 1, NRF2↑, 1, ROS↓, 2, SOD↑, 1, SOD1↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 2, LDL↓, 1,

Cell Death(tgid=5) ⓘ

Casp3↓, 1, Casp9↓, 1, Fas↓, 2, HGF/c-Met↑, 1, iNOS↓, 1, MAPK↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↑, 1, GRP78/BiP↑, 1, GRP94↑, 1,

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

p‑ERK↑, 1,

Migration(tgid=13) ⓘ

AntiAg↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX1↓, 1, COX2↓, 1, IL1β↓, 1, Inflam↓, 3, NF-kB↓, 1, TLR4↓, 2, TNF-α↓, 1,

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1, BioAv↝, 1, Dose↝, 1,

Clinical Biomarkers(tgid=22) ⓘ

BP↓, 1, GutMicro↑, 1,

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1, cardioP↑, 2, hepatoP↑, 1, neuroP↑, 1, Obesity↓, 1, RenoP↑, 1, toxicity↓, 1, Wound Healing↑, 1,
Total Targets: 50

Scientific Paper Hit Count for: HMG-CoA, Mevalonate pathway

14 Atorvastatin
5 Dipyridamole
2 Chlorogenic acid
2 Geraniol
1 Dichloroacetate
1 Aspirin
1 statins
1 Citric Acid

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#:1143  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HMG-CoA Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

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

Migration(tgid=13) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

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