Anticancer efficacies of arsenic disulfide through apoptosis induction, cell cycle arrest, and pro-survival signal inhibition in human breast cancer cells.

Arsenic disulfide, a major effective component of realgar, has been investigated for its anti-cancer potential and shown to have therapeutic efficacies in hematological and some solid tumors. However, its effect against breast cancer is rarely reported. In this study, we investigated the anti-cancer effects of As2S2 in human breast cancer cell lines MCF-7 and MDA-MB-231, and further elucidated its underlying mechanisms. As2S2 significantly inhibited cell viabilities, induced apoptosis, and led to cell cycle arrest in both cell lines with a dose- and time-dependent manner. As2S2 upregulated pro-apoptotic proteins like p53 and PARP in MCF-7 cells. Besides, As2S2 downregulated anti-apoptotic proteins like Bcl-2 and Mcl-1, as well as cell cycle-related proteins cyclin A2 and cyclin D1 in both cell lines. Of note, the expression level of cyclin B1 was downregulated in MCF-7 cells, whereas, upregulated in MDA-MB-231 cells. Moreover, As2S2 significantly inhibited the pro-survival signals in PI3K/Akt pathway in both cell lines. In conclusion, As2S2 inhibited cell viabilities, induced apoptosis and cell cycle arrest in both MCF-7 and MDA-MB-231 cell lines by regulating the expression of key proteins involved in related pathways. These results provide fundamental insights into the clinical application of As2S2 for treatment of patients with breast cancer.