Inhibitory effect of Embelin on human acute T cell lymphoma Jurkat cells through activation of the apoptotic pathway.

Abstract

It has previously been shown that Embelin inhibits proliferation, promotes apoptosis, and increases sensitivity and reduces resistance to chemotherapy drugs, in various types of tumor cells. The present study examined the effects of Embelin on the proliferation of human acute T cell lymphoma Jurkat cells. Jurkat cells were treated with various concentrations of Embelin and the effects of Embelin on the inhibition of growth of Jurkat cells were evaluated. Expression of X-linked inhibitor of apoptosis protein (XIAP); poly ADP ribose polymerase; caspase-3; caspase-8; caspase-9; the proapoptotic protein, Bax; and the antiapoptotic proteins, Bcl-xl and Bcl-2, were assessed. The results showed that Embelin significantly inhibited the growth of human acute T cell lymphoma Jurkat cells. Following treatment with 5, 10 or 20 mM Embelin for 48 h, cell viability was 82.31, 58.65 and 37.62%, respectively, which was significantly reduced compared with that of the control group and the 0.1% DMSO control group (P<0.01). Furthermore, the caspase-3 inhibitor, z-DEVD-fmk, and the caspase-9 inhibitor, Ac-LEHD-CHO, reversed this inhibitory effect. It was also shown that the apoptotic rate of cells treated with Embelin was significantly elevated. Subsequently, it was demonstrated that Embelin downregulated the expression of XIAP and the proapoptotic Bcl2 family members, Bcl-2 and Bcl-xl, while it concomitantly upregulated that of the antiapoptotic protein, Bax. These results showed that Embelin inhibited growth and induced apoptosis of Jurkat cells in vitro, by activating the endogenous caspase-dependent apoptotic pathway through inhibition of XIAP and proapoptotic Bcl-2 family members.