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A new anticancer compound, Oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through bax activation
Feng C.1; Zhou L.-Y.1; Yu T.2; Xu G.4; Tian H.-L.1; Xu J.-J.1; Xu H.-X.3; Luo K.Q.2
2012-09-15
Source PublicationInternational Journal of Cancer
ISSN00207136 10970215
Volume131Issue:6Pages:1445-1454
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 IC 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 values, regardless of the expression levels of HER2 and P-glycoprotein. In contrast, the IC 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. Copyright © 2011 UICC.

KeywordAnticancer Drug Discovery Apoptosis Bax Herbal Medicine Oblongifolin c
DOI10.1002/ijc.27365
URLView the original
Indexed BySCI
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000306735700045
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Cited Times [WOS]:32   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Hong Kong University of Science and Technology
2.Nanyang Technological University
3.Shanghai University of Traditional Chinese Medicine
4.Kunming Institute of Botany Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Feng C.,Zhou L.-Y.,Yu T.,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 C..,Zhou L.-Y..,Yu T..,Xu G..,Tian H.-L..,...&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.
MLA Feng C.,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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