Curcumin induces apoptosis by inhibiting BCAT1 expression and mTOR signaling in cytarabine‑resistant myeloid leukemia cells.

Abstract

Cytarabine is a key chemotherapy drug for treating leukemia; however, chemotherapy-induced multidrug resistance is a major cause of therapy failure or tumor recurrence. Current medical treatment strategies still cannot address the issue of multidrug resistance phenotypes in the treatment of leukemia. Curcumin counteracts tumor development by inducing apoptosis in cytarabine-resistant acute myeloid leukemia cells. Branched-chain amino acid transaminase 1 (BCAT1), an aminotransferase enzyme, acts on branched-chain amino acids. Moreover, the aberrant expression of BCAT1 has been observed in numerous cancer cells, and BCAT1 serves a critical role in the progression of myeloid leukemia. BCAT1 can interfere with cancer cell proliferation by regulating mTOR-mediated mitochondrial biogenesis and function. The present study aimed to investigate whether curcumin induces apoptosis by regulating BCAT1 expression and mTOR signaling in cytarabine-resistant myeloid leukemia cells. Four leukemia cell lines and three primary myeloid leukemia cells were treated with curcumin, and the expression and activity of BCAT1 and mTOR were investigated by reverse transcription-quantitative PCR, western blotting and α-KG quantification assay. The results demonstrated that curcumin inhibited BCAT1 expression in Kasumi-1, KG-1, HL60, cytarabine-resistant HL60, and cytarabine-resistant primary myeloid leukemia cells. Notably, tetrahydrocurcumin, a major metabolite of curcumin, and cytarabine had no inhibitory effect on BCAT1 expression. Furthermore, BCAT1 and mTOR signaling may modulate each other in cytarabine-resistant HL60 cells. The present results indicated that curcumin may induce apoptosis by inhibiting the BCAT1 and mTOR pathways. Thus, understanding the mechanism underlying curcumin-induced apoptosis in cytarabine-resistant cells can support the development of novel drugs for leukemia.