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The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells
Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan 32023
Received: 12 November 2007; in revised form: 16 November 2007 / Accepted: 21 November 2007 / Published: 27 November 2007
Abstract: Ginkgolide B, the major active component of Ginkgo biloba extracts, can bothstimulate and inhibit apoptotic signaling. Here, we demonstrate that ginkgolide B caninduce the production of reactive oxygen species in MCF-7 breast cancer cells, leading toan increase in the intracellular concentrations of cytoplasmic free Ca2+ and nitric oxide(NO), loss of mitochondrial membrane potential (MMP), activation of caspase-9 and -3,and increase the mRNA expression levels of p53 and p21, which are known to be involvedin apoptotic signaling. In addition, prevention of ROS generation by pretreatment withN-acetyl cysteine (NAC) could effectively block intracellular Ca2+ concentrationsincreases and apoptosis in ginkgolide B-treated MCF-7 cells. Moreover, pretreatment withnitric oxide (NO) scavengers could inhibit ginkgolide B-induced MMP change andsequent apoptotic processes. Overall, our results signify that both ROS and NO playedimportant roles in ginkgolide B-induced apoptosis of MCF-7 cells. Based on these studyresults, we propose a model for ginkgolide B-induced cell apoptosis signaling cascades inMCF-7 cells.
Keywords: Ginkgolide; Apoptosis; Oxidative Stress; Nitric oxide
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MDPI and ACS Style
Chan, W.-H. The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells. Int. J. Mol. Sci. 2007, 8, 1177-1195.
Chan W-H. The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells. International Journal of Molecular Sciences. 2007; 8(11):1177-1195.
Chan, Wen-Hsiung. 2007. "The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells." Int. J. Mol. Sci. 8, no. 11: 1177-1195.