Research on the effect of Flavokawain B on the proliferation and apoptosis of acute T lymphoblastic leukemia cells

Abstract

Objective To explore the effect of Flavokawain B on the proliferation and apoptosis of acute T lymphoblastic leukemia(T-ALL) cells and its preliminary mechanism. Methods After the T-ALL cell lines CEM-C7(sensitive to glucocorticoids) and MOLT-4(resistant to glucocorticoids) cells were treated with different concentrations of Flavokawain B, the influence of Flavokawain B on the growth rate and doubling time of CEM-C7 and MOLT-4 cells was observed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay, and apoptosis was analyzed by using flow cytometry. Furthermore, Wes-tern blot assay was used to detect the expressions of Bim, Bcl-2 and cleaved Caspase-9. At last, the expressions of Bim and Bcl-2 in clinical T-ALL patient samples were also detected by using Western blot assay. Results MTS assay showed that Flavokawain B significantly inhibited the cellular proliferation of T-ALL cell lines in a dose and time dependent manner(P<0.01). Flow cytometry findings revealed that Flavokawain B significantly induced the apoptosis of T-ALL cells in a dose-dependent manner(P<0.001). Western blot results indicated that Flavokawain B increased the expression of Bim and cleaved Caspase-9, and decreased the expression of Bcl-2 in T-ALL cell lines, which increased Bim and decreased Bcl-2 in clinical T-ALL patients samples, both in a dose-dependent manner. Conclusions Flavokawain B can inhibit the proliferation and induce the apoptosis of T-ALL cells by up-regulating the expression of Bim and down-regulating the expression of Bcl-2 and activating Caspase-9, whether resistant to glucocorticoids or not. Key words: T lymphoblastic leukemia, acute; Flavokawain B; Proliferation; Apoptosis