Identification and evaluation of apoptotic compounds from Garcinia oligantha

• Published in: Bioorganic & medicinal chemistry letters 2012-03, Vol.22 (6), p.2350-2353
• Main Authors: Gao, Xue-Mei, Yu, Ting, Cui, Ming-zhu, Pu, Jian-Xin, Du, Xue, Han, Quan-bin, Hu, Qiu-fen, Liu, Tian-Cheng, Luo, Kathy Qian, Xu, Hong-Xi
• Format: Article
• Language: English
• Subjects: Anticancer drug; antineoplastic agents; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; biosensors; Blotting, Western; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; cell growth; Female; fluorescence; Garcinia; Garcinia - chemistry; Garcinia oligantha; Gene Expression; Genes, Reporter; HeLa Cells; Humans; inhibitory concentration 50; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Stems - chemistry; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; spectroscopy; stems; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology; Western blotting; Xanthenes - chemistry; Xanthenes - isolation & purification; Xanthenes - pharmacology; Xanthone; Xanthones - chemistry; Xanthones - isolation & purification; Xanthones - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.01.068

Four new compounds, oliganthins A–D (1–4), and one known caged xanthone gaudichaudione H (5) were isolated from the leaves of Garcinia oligantha. All of the five compounds were evaluated for their apoptosis-inducing effects. All of them induced cell apoptosis at 10μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP using the method of Western blot. Moreover, the values of IC50 were measured for all four compounds on HeLa cells using the MTT assay. Four new compounds, oliganthins A–D (1–4), and one known caged xanthone gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The structures of the new compounds were elucidated by spectroscopic evidences. All of the five compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. All of them induced cell apoptosis at 10μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP, which is the substrate of activated caspase-3, in these compounds-treated cells using the method of Western blot. Moreover, the values of IC50 were measured for all five compounds on HeLa cells using the MTT assay. Among them, gaudichaudione H had the lowest IC50 value of 0.90μM, while the other four new compounds had IC50 values of 1.58, 1.52, 4.15, and 7.82μM, respectively. These results show that gaudichaudione H has the strongest apoptosis-inducing effect and cell growth inhibition effect among these xanthones and it may have the potential to be developed into a new anticancer agent.