Persicaline, an alkaloid from Salvadora persica, inhibits proliferation and induces apoptosis and cell-cycle arrest in MCF-7 cells

Abstract

Cancer is the second largest cause of mortality worldwide. Many natural bioactive chemicals generated from plants have favorable impacts on health, including cancer chemoprevention, compared to their manufactured counterparts. Persicaline, a novel sulfur-containing imidazoline alkaloid derived from Salvadora persica, has been shown to display promising antioxidant activity. In this study, the antiproliferative activity of persicaline was tested against different cancer cells using (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. The cell death mode and cell-cycle arrest were examined using flow cytometry analysis. In addition, the proapoptotic and molecular mechanism effects of persicaline against mammary MCF-7 cell line were explored. Furthermore, the impact of persicaline on apoptotic genes markers, generation of reactive oxygen species (ROS), and mitochondrial membrane potential were monitored. It was found that persicaline inhibits cell proliferation in a dose-dependent manner. Persicaline-treated MCF-7 cells also showed initiation of apoptotic events and G1 cell-cycle arrest. In addition, persicaline treatment led to an increase in ROS generation, Bax and caspase upregulation while the Bcl-2 was downregulated. Hence, for the first time, this study showed that persicaline causes G1 phase arrest and apoptosis induction in MCF-7 cells. Increased proapoptotic genes and ROS levels were required for the antiproliferative and apoptotic effects of persicaline.