Pomelo Peel Extract induces ROS-mediated DNA Double Stand Break and Apoptotic Death Pathway in Caco-2 Colon Cancer Cells

Abstract

Colorectal cancer (CRC) ranks among the top ten leading causes of death in the world. Beyond chemical therapy or targeted therapy, finding an alternative approach to colorectal cancer therapy is necessary. Citrus grandis (L.) Osbeck is a popular fruit cultivated worldwide; the peel is mainly discarded after consuming the fruit. However, it has also been commonly reported as folk medicine for treating several illnesses, such as cough and indigestion. In this study, Caco-2 cells were treated with different concentrations of pomelo peel extract (PPE). PPE suppressed cell viability in a dose-dependent manner at 24 and 48 h. The PPE extract showed condensed chromatin and apoptotic cells at 12, 24, and 48 h under the microscope in DAPI (4′,6-diamidino-2-phenylindole) staining. Moreover, PPE activated the apoptosis pathway by increasing the protein expression of cleaved caspase-3. In addition, it also expressed elevation of pro-apoptotic Bax and degradation of anti-apoptotic Bcl-2. In addition, it enhanced the p-Chk2 protein in arresting the cell cycle and increased the protein expression of p-Histone H2A.X. Those results suggest that PPE can reduce cell viability in Caco-2 cells through ROS production and DNA damage.