Arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells through activation of caspase-3 and inhibition of HERG channels

Abstract

Arsenic trioxide (As(2)O(3)) has been widely used to treat patients with acute promyelocytic leukemia and has also been shown to exhibit therapeutic effects on various types of solid tumors, including gastric cancer and lung carcinoma. Breast cancer is a type of solid tumor whose incidence has been increasing for many years. The present study was designed to investigate the effects of As(2)O(3) on the human breast cancer cell line MCF-7, and to explore its potential mechanisms. The MTT assay demonstrated that As(2)O(3) decreased the cellular viability of MCF-7 cells in a concentration-dependent manner. Morphological observation, the TUNEL assay and flow cytometric analysis revealed that apoptosis was involved in the process. An assay for caspase-3 activity suggested that the apoptosis was mediated through caspase-3 activation. Further investigation indicated that protein levels of the human ether-a-go-go-related gene (HERG) were markedly downregulated by As(2)O(3). Taken together, the results indicate that arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells at least in part through the activation of caspase-3 and the decrease in HERG expression.