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A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation
Author(s) -
Feng Chao,
Zhou LiYing,
Yu Ting,
Xu Gang,
Tian HongLei,
Xu JinJie,
Xu HongXi,
Luo Kathy Qian
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27365
Subject(s) - apoptosis , etoposide , hela , dna fragmentation , vinblastine , programmed cell death , in vivo , cancer research , cancer cell , cell culture , caspase 3 , biology , paclitaxel , cytochrome c , pharmacology , chemistry , microbiology and biotechnology , cell , cancer , biochemistry , chemotherapy , genetics
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 IC 50 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 IC 50 values, regardless of the expression levels of HER2 and P‐glycoprotein. In contrast, the IC 50 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.