A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation
Feng, Chao2; Zhou, Li-Ying2; Yu, Ting1; Xu, Gang3; Tian, Hong-Lei4; Xu, Jin-Jie2; Xu, Hong-Xi5; Luo, Kathy Qian1
2012-09-15
发表期刊INTERNATIONAL JOURNAL OF CANCER
ISSN0020-7136
卷号131期号:6页码:1445-1454
摘要Oblongifolin C (OC) was identified as a potent apoptosis inducer from an herbal plant, Garcinia yunnanensis, during our previous bioassay-guided drug screening. In this study, we investigated the signaling pathways through which OC activated apoptosis in HeLa cells. We also compared the IC50 values of OC with that of etoposide, paclitaxel and vinblastine in multiple cancer cell lines including HER2 and P-glycoprotein overexpressing cells. In addition, the in vivo antitumor effect of OC was studied in nude mice model. Our results showed that OC induced a caspase-dependent apoptosis by triggering a series of events in HeLa cells including Bax translocation, cytochrome c release, caspase-3 activation, chromosome fragmentation followed by caspase-8 activation, Bid cleavage and eventually cell death. Addition of a pan-caspase inhibitor or overexpression of an anti-apoptotic protein, Bcl-xL, prevented OC-induced cell death. Moreover, OC exhibited a wide anticancer spectrum in multiple cancer cell lines with comparable IC50 values, regardless of the expression levels of HER2 and P-glycoprotein. In contrast, the IC50 values of three clinical anticancer drugs, etoposide, paclitaxel and vinblastine were significantly elevated in HER2 and/or P-glycoprotein overexpressing cells. Furthermore, OC showed a similar antitumor effect but lower general toxicity than etoposide against xenografted human tumors in nude mice model. All these data suggested that OC is a promising apoptosis inducer with the potential to be developed into a clinical anticancer drug.
关键词Anticancer Drug Discovery Herbal Medicine Oblongifolin c Apoptosis Bax
资助信息Academic Research Fund (AcRF) Tier 1 grant of the Minister of Education of Singapore [M52120104]; National Natural Science Foundation of China [81173485]
DOI10.1002/ijc.27365
收录类别SCI
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000306735700045
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被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/15692
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Nanyang Technol Univ, Div Bioengn, Sch Chem & Biomed Engn, Singapore 637457, Singapore
2.Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Hong Kong, Hong Kong, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, Kunming, Yunnan, Peoples R China
4.Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China
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Feng, Chao,Zhou, Li-Ying,Yu, Ting,et al. A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation[J]. INTERNATIONAL JOURNAL OF CANCER,2012,131(6):1445-1454.
APA Feng, Chao.,Zhou, Li-Ying.,Yu, Ting.,Xu, Gang.,Tian, Hong-Lei.,...&Luo, Kathy Qian.(2012).A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation.INTERNATIONAL JOURNAL OF CANCER,131(6),1445-1454.
MLA Feng, Chao,et al."A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation".INTERNATIONAL JOURNAL OF CANCER 131.6(2012):1445-1454.
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