Apoptosis of HL-60 human leukemia cells induced by Asiatic acid through modulation of B-cell lymphoma 2 family proteins and the mitogen-activated protein kinase signaling pathway.

摘要: Abstract The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. present study aimed explore the effect chemopreventive agent asiatic acid (AA) on proliferation apoptotic rate leukemia cell line HL-60 investigated mechanisms underlying its anti-tumor activity. AA was evaluated using MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well Hoechst 33258 were used analyze cells. Furthermore, changes survivin, B-cell lymphoma 2 (Bcl-2), myeloid 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal (JNK) p38 expressions detected western blot analysis. blocked growth a dose- time-dependent manner. IC50-value 46.67 ± 5.08 µmol/l for 24 h. induced apoptosis dose-dependent manner, inhibited presence Z-DEVD-FMK, specific inhibitor caspase. anti-apoptotic proteins Bcl-2, Mcl-1 survivin downregulated Concurrently, ERK phosphorylation while JNK not affected. In conclusion, indicated that pathways, modulation Bcl-2 family key regulators response AA.