| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Butyrate — a four-carbon short-chain fatty acid produced mainly by gut microbial fermentation of dietary fiber, functioning as both a colonocyte energy substrate and a pleiotropic signaling metabolite. It is formally classified as an endogenous microbial metabolite and short-chain fatty acid; common research and delivery forms include sodium butyrate and the oral prodrug tributyrin. Standard abbreviations include butyrate, NaBu, SCFA, and TB for tributyrin. Its source is primarily the colonic microbiome–fiber axis, with highest physiological relevance in the colon lumen and colonic epithelium rather than in systemic circulation. In cancer biology, its effects are highly context-dependent: it is most mechanistically credible in colorectal and inflammation-linked gastrointestinal settings, while newer tumor-microbiome data indicate that intratumoral butyrate can also support progression in some non-colorectal contexts. Butyric acid primarily exerts its anticancer properties through two mechanisms:(i) Activation of cell-surface receptors (GPR41, GPR43 and HCAR2/GPR109A) (ii) inhibition of HDACs in different cells. butyrate paradox: butyrate promotes proliferation of normal colonocytes, it has the opposite effect on cancerous cells where it inhibits cell proliferation and also induces apoptosis Primary mechanisms (ranked):
Bioavailability / PK relevance: Butyrate is rapidly absorbed and extensively metabolized, so systemic exposure is limited and transient. Physiologic and therapeutic relevance is therefore mainly local to the colon; oral strategies that matter most are colonic-release sodium butyrate, microbiome/fiber approaches, or tributyrin-type prodrugs that improve delivery. In-vitro vs systemic exposure relevance: Many cancer-cell studies use roughly 0.5–5 mM, with some using higher concentrations. Those ranges are plausible in the colonic lumen and at the epithelial interface, where butyrate commonly reaches about 10–20 mM, but they are generally not representative of sustained plasma exposure after ordinary oral dosing. Clinical evidence status: Preclinical for direct anticancer efficacy; small early-phase human oncology studies exist for tributyrin and other butyrate-delivery approaches, but no established antitumor standard-of-care role is supported. Human evidence is stronger for GI-supportive or radiotherapy-supportive use than for tumor control. Butyrate mechanistic matrix
TSF legend: P: 0–30 min (primary/rapid effects) | R: 30 min–3 hr (acute signaling + stress responses) | G: >3 hr (gene-regulatory adaptation; phenotype outcomes) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Source: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type: effect | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring. Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate. Warburg effect (GLUT1, LDHA, HK2, and PKM2).Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export). Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) - HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: - PKM2 Inhibitors: (Shikonin) -Can reduce glycolysis - LDH Inhibitors: (Gossypol, FX11) -Reducing the conversion of pyruvate to lactate. -Inhibiting the production of ATP and NADH. - GLUT1 Inhibitors: (phloretin, WZB117) -A key transporter involved in glucose uptake. -GLUT3 Inhibitors: - PDK1 Inhibitors: (dichloroacetate) - A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure. 2.Pentose phosphate pathway: - G6PD Inhibitors: can reduce the pentose phosphate pathway 3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: - HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 4.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 5.mTOR pathway: - mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. Warburg Targeting Matrix (Cancer Metabolism)
Time-Scale Flag (TSF): P / R / G
|
| 5745- | Buty, | Microbial Oncotarget: Bacterial-Produced Butyrate, Chemoprevention and Warburg Effect |
| - | Review, | Var, | NA |
| 5737- | Buty, | Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming |
| - | in-vitro, | CRC, | HCT116 |
| 5731- | Buty, | The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | CRC, | HT29 |
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#:50 Target#:947 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid