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| Betulinic acid "buh-TOO-li-nik acid" is a natural compound with antiretroviral, anti malarial, anti-inflammatory and anticancer properties. It is found in the bark of several plants, such as white birch, ber tree and rosemary, and has a complex mode of action against tumor cells. -Betulinic acid is a naturally occurring pentacyclic triterpenoid -vitro concentrations range from 1–100 µM, in vivo studies in rodents have generally used doses from 10–100 mg/kg Precursor: Betulin, via oxidation at C-28 Lipophilicity: High (poor aqueous solubility) -half-life reports vary 3-5 hrs?. Reported half-life varies by formulation and species; several studies report multi-hour systemic persistence. BioAv -hydrophobic molecule with relatively poor water solubility. Main Cancer action -Direct mitochondrial targeting in cancer cells -Minimal effect on normal cells Key pathways -Mitochondrial membrane permeabilization -ROS-mediated apoptosis -Caspase-independent death Chemo relevance: Generally compatible, Not a redox buffer Pathways: - often induce ROS production - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ - Lowers AntiOxidant defense in Cancer Cells(Often associated with reduced redox buffering capacity in tumor cells (e.g., GSH depletion); NRF2 direction model-dependent.): NRF2↓, SOD↓, GSH↓ - May Raise AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑ Reports suggest relative sparing of normal cells and preservation of antioxidant capacity in some models - lowers Inflammation : NF-kB↓(typ), COX2↓, p38↓ (context-dependent; often stress-activated), Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : P53↑, HSP↓(model-dependent), Sp proteins↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, - inhibits glycolysis (secondary to mitochondrial stress) ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, GRP78↑(ER stress), GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, - inhibits Cancer Stem Cells in some studies : CSC↓, GLi1↓, β-catenin↓, OCT4↓, - Others: PI3K↓(typ), AKT↓(typ), JAK↓, STAT↓, β-catenin↓, AMPK↓(AMPK is often activated during metabolic stress), ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells
Time-Scale Flag (TSF): P / R / G
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| Cancer Stem Cells Phytochemicals (natural plant-derived compounds) that may affect CSCs: Curcumin — suppresses self-renewal and pathways (Wnt/Notch/Hedgehog). Resveratrol — shown to reduce CSC populations and sphere formation in multiple models. Sulforaphane (from broccoli sprouts) — reported to inhibit CSC properties and pathways; active in vitro and in vivo. EGCG (epigallocatechin-3-gallate, green tea) — reduces CSC markers and sphere formation in several cancer types. Quercetin — reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others). Berberine — shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models. Genistein (soy isoflavone) — decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models. Honokiol (Magnolia bark) — shown to eliminate or suppress CSC-like populations in oral, colon, glioma models. Luteolin — inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models. Withaferin A (from Withania somnifera / ashwagandha) — multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models. Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy Can we utilise the circadian clock to target cancer stem cells? |
| 2763- | BetA, | Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-β1 Signaling Pathway and Macrophage Polarization |
| - | in-vitro, | GC, | NA |
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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