The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells Wen-Hsiung Chan* Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan 32023
Abstract: Ginkgolide B, the major active component of Ginkgo biloba extracts, can both stimulate and inhibit apoptotic signaling. Here, we demonstrate that ginkgolide B can induce the production of reactive oxygen species in MCF-7 breast cancer cells, leading to an 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 involved in apoptotic signaling. In addition, prevention of ROS generation by pretreatment with N-acetyl cysteine (NAC) could effectively block intracellular Ca2+ concentrations increases and apoptosis in ginkgolide B-treated MCF-7 cells. Moreover, pretreatment with nitric oxide (NO) scavengers could inhibit ginkgolide B-induced MMP change and sequent apoptotic processes. Overall, our results signify that both ROS and NO played important roles in ginkgolide B-induced apoptosis of MCF-7 cells. Based on these study results, we propose a model for ginkgolide B-induced cell apoptosis signaling cascades in MCF-7 cells.
Conclusions Based on the results of the present study, we propose a possible model of ginkgolide B-induced cell apoptosis signaling in MCF-7 cells (Figure 8). Our results collectively show that both intracellular ROS and NO play critical roles in ginkgolide B-induced cell apoptosis of MCF-7 cells.
Figure 8. Scheme of events occurring during ginkgolide B-induced cell apoptosis in MCF-7 cells.
MCF-7 cells --(Ginkgolide B treatment) ------> ROS generation ------> Increase of [Ca2+]i ------>NO increases ------> Increase of p53 and p21, Loss of MMP , Caspases activation ------> Cell apoptosis