Macrocalyxin A inhibits proliferation and induces apoptosis of t (8;21) leukemia cells through mitochondrial signaling pathways and regulates AML-ETO mRNA expression

Abstract

Abstract. Progress in the last decade has improved the treatment of acute myeloid leukemia (AML); however, the treatment of AML is also demanding and better treatments are required. The present study aimed to examine the antiproliferative and proapoptotic effects of macrocalyxin A (MA), a novel deterpenid compound, on AML cells. It was identified that MA significantly inhibits kasumi-1 cell proliferation in a time-and dose-dependent manner. Furthermore, low concentrations of MA were able to induce kasumi-1 cell differentiation; however, high concentrations of MA induced kasumi-1 cell apoptosis. MA was also able to increase the expression of mitochondrial membrane protein in a dose-dependent manner while the ∆Ψm was reduced. Additionally, Bad expression in kasumi-1 cells was increased when treated with MA, indicating that the intrinsic apoptotic pathway may be important in MA-induced kasumi-1 cell apoptosis, where the mitochondrial permeability transition pore is opened and the ΔΨm is reduced. In addition, it was demonstrated that AML-ETO mRNA may also be important in MA-induced apoptosis.