Medicinal Chemistry

2-tert-butyl-1,4-benzoquinone Induces Apoptosis in Chronic Myeloid Leukemia Cells Resistant to Imatinib via Inducing Caspase-Dependent Bcr- Abl Downregulation

Abstract

Xianping Shi, Xiaoying Lan, Xiaofen Li, Xin Chen, Bing Z. Carter, Xuejun Wang and Jinbao Liu

Bcr-Abl-T315I mutation-induced imatinib (IM) resistance remains a major challenge for clinical management of chronic myelogenous leukemia (CML). Therefore it is imperative to search for novel agents to overcome IMresistance. 2-Tert-butyl-1,4-benzoquinone (TBQ) is an oxidation product of 2-tert-Butylhydroquinone (TBHQ) which has been developed as a food additive and proves to be a strong antioxidant. Previous studies showed that TBQ has cytotoxic effect on different types of neoplastic cells. Our recent study confirmed that TBQ induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of IM-resistant primary monocytes from CML patients. Here we further report that TBQ-induced caspase activation is required for the downregulation of Bcr-Abl and apoptotic cell death in both IM-resistant and IM-sensitive CML cells. These findings suggest an alternative strategy to overcome IM resistance by enhancing Bcr-Abl downregulation with TBQ.