Characterization of proapoptotic compounds from the bark of Garcinia oblongifolia

Twenty compounds from Garcinia oblongifolia were screened for proapoptotic activity using FRET-based HeLa-C3 sensor cells. Among them, oblongifolins F and G (1 and 2), 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran[7,6-b]xanthone (3), nigrolineaxanthone T (4), and garcicowin B (5) showed significant proapoptotic activity at a concentration of 10 μM. Bioassessments were then performed to evaluate the potential of these compounds for therapeutic application. All five compounds showed significant cytotoxicity and caspase-3-activating ability in cervical Cancer HeLa cells, with compounds 1 and 2 having the highest potencies. All five compounds specifically induced caspase-dependent Apoptosis, which could be prevented by the pan-caspase inhibitor zVAD-fmk. In particular, 3 induced Apoptosis through mitotic arrest. Compounds 1-5 displayed similar IC50 values (3.9-16.5 μM) against the three Cancer cell lines HeLa, MDA-MB-435, and HepG2. In addition, compounds 1, 2, and 4 exhibited similar and potent IC50 values (2.4-5.1 μM) against several breast and colon Cancer cell lines, including those overexpressing either HER2 or P-glycoprotein. HER2 and P-glycoprotein are known factors that confer resistance to Anticancer drugs in Cancer cells. This is the first study on the cytotoxicity, caspase-3-activing ability, and specificity of proapoptotic compounds isolated from G. oblongifolia in HeLa cells. The potential application of these compounds against HER2- or P-glycoprotein-overexpressing Cancer cells was investigated.