Characterization of Proapoptotic Compounds from the Bark of Garcinia oblongifolia

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• 作者：Chao Feng ; Sheng-Xiong Huang ; Xue-Mei Gao ; Hong-Xi Xu ; Kathy Qian Luo
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：May 23, 2014
• 年：2014
• 卷：77
• 期：5
• 页码：1111-1116
• 全文大小：376K
• 年卷期：v.77,no.5(May 23, 2014)
• ISSN：1520-6025

文摘

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 渭M. 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鈥?b>5 displayed similar IC₅₀ values (3.9鈥?6.5 渭M) 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鈥?.1 渭M) 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.