HCAR2 Cancer Research Results
HCAR2, HCAR2/GPR109A: Click to Expand ⟱
Scientific Papers found: Click to Expand⟱
*GutMicro↑, Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD)
*other↑, (2) stimulates growth and proliferation of normal intestinal epithelial cells;
*Inflam↓, (3) inhibits inflammation;
*ROS↓, (4) inhibits oxidative stress;
AntiCan↑, (8) inhibits colon carcinogenesis
HCAR2↑, three cell-surface G-protein-coupled receptors, GPR41, GPR43, and GPR109A, are targets for butyrate [1,2].
HDAC↓, butyrate also has intracellular actions (HDAC inhibition),
HCAR2↑, Another major GPCR activated by butyrate is GPR109A (
Inflam↓, anti-inflammatory properties of butyrate are also achieved through inhibition of the production of proinflammatory enzymes and cytokines
HDAC↓, Butyrate functions as an HDAC inhibitor
*IFN-γ↓, animal studies reported that the proinflammatory cytokines IFN-γ, TNF-α, IL-1β, IL-6, and IL-8 are inhibited, whereas IL-10 and TGF-β are upregulated in response to butyrate
*TNF-α↓,
*IL1β↓,
*IL6↓,
*IL8↓,
*IL10↑,
*TNF-β↑,
*NF-kB↓, butyrate is at least in part due to inhibition of the activation of a transcription factor known as NF-κB (
*ROS↓, by rescuing the redox machinery and controlling reactive oxygen species,
PPARγ↓, Further studies also showed that butyrate is capable of activating PPAR-γ (67), which is a member of the nuclear hormone receptor family and highly expressed in colonic epithelial cells,
Weight↓, although a large body of evidence has suggested the effect of butyrate on alleviating high fat diet–induced obesity and insulin resistance, a few studies showed an opposite effect.
*eff↓, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production
Dose↝, Several studies have found that the ratio of acetate to propionate to butyrate in the colon of healthy individuals (regardless of region) has been found to be approximately 60:20:20 [2,3].
eff↑, An appropriate polysaccharide-to-protein ratio appears crucial for maintaining gut microbial homeostasis and facilitating butyrate generation.
HDAC↓, butyrate is a classic HDAC inhibitor that increases the acetylation level of histone H3 and H4,
ac‑H3↓,
ac‑H4↓,
*HCAR2↑, butyrate is produced by the gut microbiota at high concentrations (10–20 mM) and acts as an endogenous agonist of GPR109A.
*Inflam↓, When butyrate activates GPR109A on colonocytes, it triggers intracellular signaling cascades, promotes the secretion of the anti-inflammatory cytokine IL-18,
*ROS↓, Moreover, butyrate reduces the level of reactive oxygen species by activating the Nrf2 antioxidant pathway and enhancing glutathione (GSH) synthesis, and alleviate stress damage to the to intestinal barrier and immune cells.
*NRF2↑,
*GSH↑,
*CLDN1↑, Butyrate also enhances epithelial barrier function by upregulating the expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 in intestinal epithelial cells.
*ZO-1↑,
IL1β↓, rucial role in repairing and strengthening the intestinal barrier by downregulating the transcription of pro-inflammatory genes, including IL-1β, IL-6, and COX-2,
IL6↓,
COX2↓,
eff↝, Different types of monosaccharides significantly influence the efficiency of butyrate production due to their distinct chemical properties and microbial utilization mechanisms.
eff↑, After entering the colon, polysaccharides serve as fermentation substrates for gut microbiota and are broken down into butyrate.
other↝, A central challenge in current research on gut microbiota and butyrate production lies in determining the optimal dietary ratio of polysaccharides to proteins.
GutMicro↑, Butyrate, a short-chain fatty acid, is generated through gut microbial fermentation of dietary fiber.
*Inflam↓, Butyrate, a primary anti-inflammatory SCFA, exhibits a multifaceted role in mitigating inflammation
*IL6↓, It inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, TNF-α and IL-17, which helps to prevent colon cancer
*TNF-α↓,
*IL17↓,
*IL10↑, while promoting IL-10 production
*ROS↝, regulates the production of reactive oxygen species (ROS)
COX2↓, butyrate has been observed to suppress inflammation by inhibiting the expression of cyclooxygenase-2 mRNA in colonic tissues (60).
NLRP3↓, butyrate exhibits the highest efficiency in the negative regulation of NLRP3
Imm↑, Enhancement of the immunotherapeutic effect
HDAC↓, Inhibition of HDAC activity in cells
TumCCA↑, Butyrate has been found to induce cell cycle arrest in the G0/G1 phase in a dose-dependent manner in vitro in numerous tumors, including colon, liver, lung and bladder cancer,
Apoptosis↑, butyrate-induced apoptosis is accompanied by elevated ROS levels and caspase activity (126)
ROS↑,
Casp↑,
mtDam↑, suggests that ROS can induce mitochondrial membrane damage, release Cyt c from damaged mitochondria, and enhance apoptosis via the Cyt c/caspase-3 pathway
Cyt‑c↑,
eff↑, Clostridium butyricum is an anaerobic bacterium classified as a probiotic due to its production of butyric acid (139)
chemoP↑, butyrate not only alleviates the side effects associated with conventional chemotherapeutic agents such as oxaliplatin, irinotecan and 5-fluorouracil (149-151), but it also enhances the efficacy of both chemotherapy and immunotherapy
ChemoSen↑,
eff↑, metformin has been demonstrated to enhance the biosynthesis of butyrate while concurrently inhibiting the progression of CRC
RadioS↑, Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone.
HCAR2↑, Activation of cell-surface receptors (GPR41, GPR43 and GPR109A);
GutMicro↑, Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process
HCAR2↑, GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation.
AntiCan↑, Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner.
Inflam↓, We hypothesized that GPR109A has an anti-inflammatory role in the colon.
IL18↑, Butyrate or Niacin Induces IL-18 Expression in Colonic Epithelium in a Gpr109a-Dependent Manner
HCAR2↑, Millimolar concentrations of butyrate are needed to activate the receptor.
other↓, The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines.
Apoptosis↑, Re-expression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate.
HDAC↓, Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation.
Bcl-2↓, primary changes in this apoptotic process include downregulation of Bcl-2, Bcl-xL, and cyclin D1, and upregulation of death receptor pathway.
Bcl-xL↓,
cycD1/CCND1↓,
DR5↑,
NF-kB↓, In addition, GPR109A/butyrate suppresses NF-κB activation in normal and cancer colon cell lines as well as in normal mouse colon.
GutMicro↑, Gut bacteria play a critical role in the prevention of colon cancer and inflammatory bowel disease
SLC12A5↝, We have shown previously that butyrate induces apoptosis in colon cancer cell lines if SLC5A8, a butyrate transporter, is expressed in these cells and that the process is associated with inhibition of HDACs
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 ⓘ
ROS↑, 1,
Mitochondria & Bioenergetics ⓘ
mtDam↑, 1,
Core Metabolism/Glycolysis ⓘ
PPARγ↓, 1,
Cell Death ⓘ
Apoptosis↑, 2, Bcl-2↓, 1, Bcl-xL↓, 1, Casp↑, 1, Cyt‑c↑, 1, DR5↑, 1,
Kinase & Signal Transduction ⓘ
HCAR2↑, 5,
Transcription & Epigenetics ⓘ
ac‑H3↓, 1, ac‑H4↓, 1, other↓, 1, other↝, 1,
Cell Cycle & Senescence ⓘ
cycD1/CCND1↓, 1, TumCCA↑, 1,
Proliferation, Differentiation & Cell State ⓘ
HDAC↓, 5,
Barriers & Transport ⓘ
SLC12A5↝, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 2, HCAR2↑, 5, IL18↑, 1, IL1β↓, 1, IL6↓, 1, Imm↑, 1, Inflam↓, 2, NF-kB↓, 1,
Protein Aggregation ⓘ
NLRP3↓, 1,
Drug Metabolism & Resistance ⓘ
ChemoSen↑, 1, Dose↝, 1, eff↑, 4, eff↝, 1, RadioS↑, 1,
Clinical Biomarkers ⓘ
GutMicro↑, 3, IL6↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 2, chemoP↑, 1, Weight↓, 1,
Total Targets: 37
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
GSH↑, 1, NRF2↑, 1, ROS↓, 3, ROS↝, 1,
Kinase & Signal Transduction ⓘ
HCAR2↑, 1,
Transcription & Epigenetics ⓘ
other↑, 1,
Migration ⓘ
CLDN1↑, 1, ZO-1↑, 1,
Immune & Inflammatory Signaling ⓘ
HCAR2↑, 1, IFN-γ↓, 1, IL10↑, 2, IL17↓, 1, IL1β↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 3, NF-kB↓, 1, TNF-α↓, 2, TNF-β↑, 1,
Drug Metabolism & Resistance ⓘ
eff↓, 1,
Clinical Biomarkers ⓘ
GutMicro↑, 1, IL6↓, 2,
Total Targets: 22
Scientific Paper Hit Count for: HCAR2, HCAR2/GPR109A
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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