Characterization of Proapoptotic Compounds from the Bark of <i>Garcinia oblongifolia</i>

Twenty compounds from <i>Garcinia oblongifolia</i> were screened for proapoptotic activity using FRET-based HeLa-C3 sensor cells. Among them, oblongifolins F and G (<b>1</b> and <b>2</b>), 1,3,5-trihydroxy-13,13-dimethyl-2<i>H</i>-pyran­[7,6-<i>b</i>]­xanthone (<b>3</b>), nigrolineaxanthone T (<b>4</b>), and garcicowin B (<b>5</b>) 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 <b>1</b> and <b>2</b> 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, <b>3</b> induced apoptosis through mitotic arrest. Compounds <b>1</b>–<b>5</b> displayed similar IC₅₀ values (3.9–16.5 μM) against the three cancer cell lines HeLa, MDA-MB-435, and HepG2. In addition, compounds <b>1</b>, <b>2</b>, and <b>4</b> 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 <i>G. oblongifolia</i> in HeLa cells. The potential application of these compounds against HER2- or P-glycoprotein-overexpressing cancer cells was investigated