Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway

Reactive oxygen species (ROS) cause oncogenic mutations through direct interaction with DNA. Carvedilol (CAR) exhibits antioxidative activity, and pre‑clinical studies have identified that CAR may prevent malignant transformation in certain carcinogenic models. This suggests that CAR may be a potential agent in cancer prevention. In the present study, non‑cancerous MCF‑10A cells were used as a model to investigate the chemopreventive effect of CAR on benzo(a)pyrene (BaP)‑induced cellular carcinogenesis. It was identified that CAR had the ability to eliminate BaP‑induced ROS production and subsequent DNA damage. CAR/BaP activated the ROS‑mediated phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)Thr308 signaling pathway, whereas the effectors of the PI3K/AKT signaling pathway, murine double minute 2 (MDM2) and p53Ser15, served important functions in the BaP/CAR‑mediated MCF10A cellular transformation. The results of the present study indicated that CAR may be a novel chemopreventive agent, notably in the prevention of estrogen receptor‑negative breast cancer. The antioxidant effects of CAR may contribute to its chemopreventive activity.