23-Hydroxybetulinic acid

23-Hydroxybetulinic acid (Anemosapogenin) is an orally active triterpenoid with broad-spectrum anticancer activity. 23-Hydroxybetulinic acid reduces the levels of Bcl-2 and survivin, elevates the level of Bax, promotes the cleavage/activation of caspase-3 and caspase-9, and induces apoptosis via the endogenous mitochondrial pathway involving cytochrome C release and mitochondrial membrane potential disruption. 23-Hydroxybetulinic acid arrests the cell cycle at S and G1 phases, inhibits cancer cell proliferation, blocks the MAPK signaling pathway, regulates MMP2, and induces autophagic apoptosis by upregulating beclin-1. 23-Hydroxybetulinic acid inhibits the activity and efflux function of P-gp, increases the intracellular accumulation of chemotherapeutic drugs, and synergistically enhances cytotoxicity with Doxorubicin (HY-15142). 23-Hydroxybetulinic acid inhibits the phosphorylation and nuclear translocation of STAT6, blocks M2 macrophage polarization, and reduces M2 macrophage-mediated apoptosis resistance of colon cancer cells. 23-Hydroxybetulinic acid can be used in related studies on chronic myeloid leukemia, hepatocellular carcinoma, sarcoma 180, multidrug-resistant breast cancer, leukemia, Doxorubicin-induced cardiotoxicity, and colorectal cancer^{[1][2][3][4][5][6][7]}. In Vitro:23-Hydroxybetulinic acid (0-300 μM; 48 h) potently inhibits proliferation of human chronic myelogenous leukemia K562 cells (IC₅₀ = 39.9 μM) and exhibits lower cytotoxicity against B16, HeLa, and HUVEC cells^[1].
23-Hydroxybetulinic acid (0-80 μM; 24 h) induces concentration-dependent S phase cell cycle arrest in human chronic myelogenous leukemia K562 cells after 24 h of treatment, with 80 μM HBA increasing S phase cells to 52.34%^[1].
23-Hydroxybetulinic acid (20-80 μM; 24 h) induces concentration-dependent apoptosis in human chronic myelogenous leukemia K562 cells after 24 h of treatment, as detected by Hoechst33342/PI dual staining^[1].
23-Hydroxybetulinic acid (20-80 μM; 24 h) significantly disrupts mitochondrial membrane potential in human chronic myelogenous leukemia K562 cells after 24 h of treatment, with 80 μM HBA reducing the red/green fluorescence ratio to 0.38^[1].
23-Hydroxybetulinic acid (10-80 μM; 24 h) triggers the intrinsic (mitochondrial) apoptosis pathway in human chronic myelogenous leukemia K562 cells after 24 h of treatment, via concentration-dependent modulation of pro- and anti-apoptotic proteins and activation of caspases^[1].
23-Hydroxybetulinic acid (1.25-20 μM; 48-72 h) inhibits viability of Huh-7, Hep3B, and Li-7 human HCC cells in a time- and concentration-dependent manner, with the strongest effect in Huh-7 cells at 20 μM for 72 h^[2].
23-Hydroxybetulinic acid (1.25-20 μM; 2-3 weeks) inhibits colony formation of Huh-7, Hep3B, and Li-7 human HCC cells over 2-3 weeks, with the strongest effect in Huh-7 cells^[2].
23-Hydroxybetulinic acid (5-20 μM; 48 h) promotes apoptosis of human HCC Huh-7 cells after 48 h in a concentration-dependent manner, and this effect is reversed by Bcl-2 overexpression^[2].
23-Hydroxybetulinic acid (5-20 μM) modulates apoptosis-related protein expression in human HCC Huh-7 cells, upregulating Bax and downregulating Bcl-2 and cleaved caspase-3 in a concentration-dependent manner^[2].
23-Hydroxybetulinic acid (5-20 μM) modulates migration/invasion and MAPK pathway-related protein expression in human HCC Huh-7 cells, decreasing MMP2, MMP9, p-MEK1/2, and p-ERK1/2 while increasing TIMP2 in a concentration-dependent manner^[2].
23-Hydroxybetulinic acid (5-20 μM; 48 h) inhibits migration invasionof human HCC Huh-7 cells after 48 h in a concentration-dependent manner^[2].
23-Hydroxybetulinic acid (48 h) dose-dependently inhibits the growth of NCI-H460, SGC7901, HepG2, and sarcoma 180 cells with average IC₅₀ values of 49.2 μM, 49.1 μM, 306.4 μM, and 28.0 μM, respectively^[3].
23-Hydroxybetulinic acid (0.2-20 μM; 48 h) dose-dependently increases ADR cytotoxicity to P-gp-overexpressing MCF-7/ADR human breast carcinoma cells, reducing cell survival^[4].
23-Hydroxybetulinic acid (0.2-20 μM; 48 h) dose-dependently increases VCR cytotoxicity to P-gp-overexpressing MCF-7/ADR human breast carcinoma cells, reducing cell survival^[4].
23-Hydroxybetulinic acid (2-20 μM) dose-dependently increases ADR-induced apoptosis in P-gp-overexpressing MCF-7/ADR human breast carcinoma cells^[4].
23-Hydroxybetulinic acid (0.2-20 μM; 1 h) dose-dependently increases intracellular ADR accumulation in P-gp-overexpressing MCF-7/ADR human breast carcinoma cells^[4].
23-Hydroxybetulinic acid (0.2-20 μM; 1 h) dose-dependently increases intracellular VCR accumulation in P-gp-overexpressing MCF-7/ADR human breast carcinoma cells^[4].
23-hydroxybetulinic acid (6.25-100 μM; 6, 12, 24, 48 h) potently inhibits HL-60 cell proliferation in a dose- and time-dependent manner, with an IC₅₀ of 20.12 μM at 48 h^[5].
23-hydroxybetulinic acid (12.5 μM; 24 h) induces formation of autophagic vacuoles in HL-60 cells^[5].
23-hydroxybetulinic acid (12.5-50 μM; 24 h) arrests HL-60 cells at the G1 phase of the cell cycle, with increasing G1 phase occupancy at higher concentrations^[5].
23-hydroxybetulinic acid (12.5-50 μM; 6, 12, 24 h) induces autophagic apoptosis in HL-60 cells in vitro in a time- and dose-dependent manner, with rates ranging from 11.60% to 78.73% across tested concentrations and times^[5].
23-hydroxybetulinic acid upregulates beclin-1 mRNA expression in HL-60 cells in vitro in a dose-dependent manner^[5].
23-Hydroxybetulinic acid (0.2-20 μM; 24 h) concentration-dependently reduces Doxorubicin-induced cytotoxicity in rat H9c2 cells, increasing the IC₅₀ of Doxorubicin to 12.94, 17.67, and 26.55 μM at concentrations of 0.2, 2, and 20 μM (for 24 h) respectively^[6].
23-Hydroxybetulinic acid (2.5-40 μM; 48 h) is non-toxic to THP-1-derived M0 macrophages at concentrations up to 20 μM after 48 h of incubation^[7].
23-Hydroxybetulinic acid (10-20 μM; 48 h) concentration-dependently inhibits IL-4-induced M2 polarization of THP-1-derived macrophages, as measured by reduced CD206 expression after 48 h of incubation^[7].
23-Hydroxybetulinic acid (10-20 μM; 48 h) concentration-dependently downregulates mRNA levels of M2-associated genes (CD206, Arg1, IL-10, CCL2) in IL-4-stimulated THP-1-derived macrophages after 48 h of incubation^[7].
23-Hydroxybetulinic acid (10-20 μM; 48 h) concentration-dependently inhibits IL-4-induced STAT6 phosphorylation and nuclear translocation in THP-1-derived macrophages after 48 h of incubation, via direct binding to STAT6^[7].
23-Hydroxybetulinic acid (20 μM; 48 h) inhibits IL-4-induced M2 polarization of THP-1-derived macrophages in a STAT6-dependent manner after 48 h of incubation with IL-4^[7].
23-Hydroxybetulinic acid (10-20 μM; 48 h) concentration-dependently inhibits IL-4-induced IL-10 secretion by THP-1-derived macrophages, as measured in conditioned medium after 72 h of serum-free culture following 48 h of 23-HBA incubation^[7].
23-Hydroxybetulinic acid (20 μM; 48 h) inhibits the IL-10/STAT3/Bcl-2 signaling pathway in 5-FU-treated SW480 colorectal cancer cells cultured in conditioned medium from 23-HBA-treated macrophages, after 48 h of 5-FU incubation^[7]. In Vivo:23-Hydroxybetulinic acid (10-20 mg/kg/day; daily; 4 weeks) dose-dependently suppresses hepatocellular carcinoma tumor growth, lung metastasis, and immunosuppression in nude mice, with 20 mg/kg producing near-complete elimination of lung metastases, while showing no obvious toxic effects^[2].
23-Hydroxybetulinic acid (20-100 mg/kg; i.g.; daily; 7 consecutive days; 1 hour prior to Doxorubicin (HY-15142) when in combination) alone has no significant in vivo antitumor activity in sarcoma 180-bearing mice, but when co-administered with doxorubicin, it produces synergistic antitumor effects (52% and 59% tumor weight reduction at 20 mg/kg and 100 mg/kg, respectively), increases intra-tumor doxorubicin accumulation, inhibits Doxorubicin-induced P-gp up-regulation, and alleviates Doxorubicin-induced cardiotoxicity^[3].
23-Hydroxybetulinic acid (20-80 mg/kg/day; i.g.; daily) dose-dependently alleviates Doxorubicin-induced cardiotoxicity in male Balb/c mice, with the 80 mg/kg/day oral dose reducing heart Doxorubicin accumulation by 46.52% and improving left ventricular ejection fraction to 75.68%^[6].
23-Hydroxybetulinic acid (7.5-15 mg/kg; i.p.; daily) inhibits M2 macrophage polarization via STAT6 signaling in mice, slightly reduces colorectal tumor weight alone, and enhances 5-Fluorouracil (5-FU) (HY-90006)'s anti-tumor efficacy by approximately 80% when co-administered, without causing obvious toxicity^[7].