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《Chinese Traditional and Herbal Drugs》 2018-01
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Preparative isolation of graphislactone A from the fruits of Sinopodophyllum hexandrum and its antitumor action mechanism

GAO Mei-ling;SUN Yan-jun;FENG Wei-sheng;FU Lu;GUAN Yan-bin;ZHANG Yan-li;GONG Jian-hong;CHEN Hui;LI Xiao-kun;WANG Yan-zhi;Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine;School of Pharmacy, Henan University of Traditional Chinese Medicine;  
Objective To establish the preparative isolation technique of grahislactone A from the fruits of Sinopodophyllumhexandrum, and to investigate the action mechanism for apoptosis induction of graphislactone A in MCF-7/ADR cell line(human breast adencarcinoma cell line). Methods The fruits of S. hexandrum were extracted under ultrasound by Et OAc. Graphislactone A was enriched by silica gel column chromatography, and then purified by recrystallization. The cytotoxic activities of graphislactone A were tested against MCF-7 and MCF-7/ADR cell lines by MTT. The apoptosis of MCF-7/ADR cell line was evaluated by flow cytometry. RT-PCR was used to detect the expression of apoptosis-related genes in MCF-7/ADR cell line. Expression of P-gp in MCF-7/ADR cell line was investigated by western blotting. Results Graphislactone A was isolated from the fruits of S. hexandrum, which showed the potent cytotoxic activities against MCF-7 and MCF-7/ADR cell lines, with IC50 values of 2.38 and 9.35 μmol/L, respectively. With the increased dose of graphislactone A, the expression levels of p53, bax, caspase-3 genes were up-regulated, while bcl-2 and P-gp down-regulated in MCF-7/ADR cell line. Conclusion Graphislactone A as phenolic compoundswas firstly found in higher plants. The preparative isolation has the advantages of high-efficiency, high sample recovery, and high-purity compared with etoposide. Graphislactone A showed strong cytotoxic activities and apoptosis induction action in MCF-7 and MCF-7/ADR cell line.
【Fund】: 国家自然科学基金资助项目(31300284);; 河南中医药大学省属高校基本科研业务专项资金项目(2014KYYWF-QN26);河南中医药大学科技创新人才支持计划(2016XCXRC01);; 河南省高等学校青年骨干教师资助计划(2015GGJS-096)
【CateGory Index】: R284;R285.5
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