Cytotoxic, Antiproliferative and Pro-apoptotic Activities of Spirobisindole Alkaloids from the Philippine Medicinal Plant Voacanga globosa

Abstract

Cancer remains a public health burden which is currently exacerbated by the occurrence of chemotherapeutic resistance and adverse effects associated with present drugs. Owing to their structural diversity and well-established pharmaceutical activities, natural products have been tapped in anticancer drug discovery. Herein, we investigated the cytotoxic and antiproliferative activities of spirobisindole alkaloids from the Philippine medicinal plant Voacanga globosa, including the pro-apoptotic activity of the most potent alkaloid. Previously isolated alkaloids globospiramine (1), deoxyvobtusine (2) and vobtusine lactone (3) were subjected to in vitro MTT and CellTiter Blue assays. Alkaloids 1-3 showed cytotoxicity and antiproliferative activities against tested cell lines (L929, KB3.1, A431, MCF-7, A549, PC-3, and SKOV-3) with 1 being the most biologically active. Western blot analysis revealed 1 promoted increased expression of cleaved caspase-3 and PARP, which are indicators that the treated cancer cells underwent the caspase-dependent apoptosis. Overall, our study demonstrated the anticancer potentials of spirobisindole alkaloids, especially globospiramine (1), from Voacanga globosa. The pro-apoptotic activity of globospiramine (1) is also reported.