Guttiferone BL from the Fruits of Allanblackia gabonensis Induces Mitochondrial-Dependent Apoptosis in PA-1 Ovarian Cancer Cells

Despite the recent advancement of treatment strategies, cancer ranks 2(nd) among the causes of death globally. Phytochemicals have gained popularity as an alternate therapeutic strategy due to their nontoxic nature. Here, we have investigated the anticancer properties of guttiferone BL (GBL) along with four known compounds previously isolated from Allanblackia gabonensis. The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The study was extended for the assessment of the effect of GBL in PA-1 cells apoptosis induction, cell cycle distribution, and change in mitochondrial membrane potential using flow cytometry, Western blot analysis, and real-time PCR. Among the five tested compounds, GBL displayed significant antiproliferative effects against all tested human cancer cells (IC(50) < 10μM). Moreover, GBL exhibited no significant cytotoxicity towards normal ovarian epithelial cell line (IOSE 364) up to 50 μM. GBL induced sub-G(0) cell cycle arrest and significant upregulation of cell cycle regulatory proteins of ovarian cancer cell PA-1. Furthermore, GBL induced its apoptosis as depicted by the accumulation of cells both at the early and late apoptotic phase in Annexin V/PI assay. In addition, it decreased the PA-1 mitochondrial membrane potential and promoted upregulation of caspase-3, caspase-9, and Bax and downregulation of Bcl-2. GBL also showed a dose-dependent inhibition of PA-1 migration. Altogether, this study reveals that guttiferone BL, studied herein for the first time, exhibits efficient antiproliferative activity by the induction of apoptosis through the mitochondrial-dependent pathway. Its investigation as a therapeutic agent against human cancers especially ovarian cancer should be envisaged.