Dioscin induces caspase-independent apoptosis through activation of apoptosis-inducing factor in breast cancer cells

Title
Dioscin induces caspase-independent apoptosis through activation of apoptosis-inducing factor in breast cancer cells
Author(s)
이태진김은애장지훈이윤한[이윤한]성언기송인환김주영손호용[손호용]김수지
Keywords
DOWN-REGULATION; DNA-DAMAGE; C-FLIP; DEATH; PATHWAYS; CHEMORESISTANCE; MITOCHONDRIA; GENERATION; MECHANISM; CARCINOMA
Issue Date
201407
Publisher
SPRINGER
Citation
APOPTOSIS, v.19, no.7, pp.1165 - 1175
Abstract
Dioscin, a saponin extracted from the roots of Polygonatum zanlanscianense, shows several bioactivities such as antitumor, antifungal, and antiviral properties. Although, dioscin is already known to induce cell death in variety cancer cells, the molecular basis for dioscin-induced cell death was not definitely known in cancer cells. In this study, we found that dioscin treatment induced cell death in dose-dependent manner in breast cancer cells such as MDA-MB-231, MDA-MB-453, and T47D cells. Dioscin decreased expressions of Bcl-2 and cIAP-1 proteins, which were down-regulated at the transcriptional level. Conversely, Mcl-1 protein level was down-regulated by facilitating ubiquitin/proteasome-mediated Mcl-1 degradation in dioscin-treated cells. Pretreatment with z-VAD fails to attenuate dioscin-induced cell death as well as caspase-mediated events such as cleavages of procaspase-3 and PARP. In addition, dioscin treatment increased the population of annexin V positive cells and induced DNA fragmentation in a dose-dependent manner in MDA-MB-231 cells. Furthermore, apoptosis inducing factor (AIF) was released from the mitochondria and translocated to the nucleus. Suppression in AIF expression by siRNA reduced dioscin-induced apoptosis in MDA-MB-231 cells. Taken together, our results demonstrate that dioscin-induced cell death was mediated via AIF-facilitating caspase-independent pathway as well as down-regulating anti-apoptotic proteins such as Bcl-2, cIAP-1, and Mcl-1 in breast cancer cells.
URI
http://hdl.handle.net/YU.REPOSITORY/31535http://dx.doi.org/10.1007/s10495-014-0994-z
ISSN
1360-8185
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의과대학 > 해부학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
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