Molecules and Cells

, Volume 33, Issue 5, pp 517–524

Betulinic acid induces Bax/Bak-independent cytochrome c release in human nasopharyngeal carcinoma cells

Article

DOI: 10.1007/s10059-012-0022-5

Cite this article as:
Liu, Y. & Luo, W. Mol Cells (2012) 33: 517. doi:10.1007/s10059-012-0022-5

Abstract

Betulinic acid (BetA) is an effective and potential anticancer chemical derived from plants. BetA can kill a broad range of tumor cell lines, but has no effect on untransformed cells. The chemical also kills melanoma, leukemia, lung, colon, breast, prostate and ovarian cancer cells via induction of apoptosis, which depends on caspase activation. However, no reports are yet available about the effects of BetA on nasopharyngeal carcinoma (NPC), a widely spread malignancy in the world, especially in East Asia. In this study, we first showed that BetA can effectively kill CNE2 cells, a cell line derived from NPC. BetA-induced CNE2 apoptosis was characterized by typical apoptosis hallmarks: caspase activation, DNA fragmentation, and cytochrome c release. Overexpression of Bcl-2 and Bcl-xL could partially prevent apoptosis caused by BetA. Moreover, Bax was not activated during the induction of apoptosis. Bax/Bak knockdown and wild-type CNE2 cells showed the same kinetics of cytochrome c release. We then showed that BetA may impair mitochondrial permeability transition pores (mPTPs), which may partially contribute to cytochrome c release. These observations suggest that BetA may serve as a potent and effective anticancer agent in NPC treatment. Further exploration of the mechanism of action of BetA could yield novel breakthroughs in anti-cancer drug discovery.

Keywords

apoptosisBetulinic acidcytochrome c releasemPTPnasopharyngeal carcinoma

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2012

Authors and Affiliations

  1. 1.E.N.T DepartmentThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing CityChina