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Title: A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation
Authors: Feng, Chao
Zhou, Liying
Yu, Ting
Xu, Gang
Tian, Hong-Lei
Xu, Jin-Jie
Xu, Hong-Xi
Luo, Kathy Qian
Issue Date: 2011
Source: Feng, C., Zhou, L.-Y., Yu, T., Xu, G., Tian, H.-L., Xu, J.-J., Xu, H.-X., & Luo, K. Q. (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.
Series/Report no.: International journal of cancer
Abstract: 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.
ISSN: 0020-7136
DOI: 10.1002/ijc.27365
Fulltext Permission: none
Fulltext Availability: No Fulltext
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