Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Weiwei Zhang • Zhiping Wang • Tongsheng Chen
- چاپ و سال / کشور: 2010
Description
Curcumol isolated from Rhizoma Curcumae, a common traditional Chinese medicine, has been reported to possess antitumor effects, but little is known about the molecular mechanism. The current study tried to explore the molecular mechanism of curcumol-induced cell death in human lung adenocarcinoma (ASTC-a-1) cells. Cell counting kit (CCK-8) assay, fluorescence resonance energy transfer (FRET), confocal fluorescence microscopy imaging, emission spectral analysis, and flow cytometry (FCM) technologies were used to assess the characteristics of curcumol-induced cell death. FCM analysis showed that curcumol induced G2/M phase arrest, nuclear fragmentation and phosphatidylserine externalization, implying that curcumol dominantly induced apoptotic cell death. Dynamical imaging showed that curcumol induced a rapid translocation of Bax from cytosol into mitochondria within 6 h, leading to a rapid dissipation of mitochondrial membrane potential (DWm), implying that mitochondria play an important role in the curcumol-induced apoptosis. The fact that Z-VAD-fmk, a broad-spectrum inhibitor of caspases, did not reduce the curcumol-induced apoptosis showed that caspases were not involved in curcumol-induced apoptosis, which was further verified by monitoring the caspase-3 activation inside living cells stably expressing SCAT3, a FRET plasmid. Collectively, we for the first time demonstrated that curcumol induced cell death in a dominant apoptotic fashion via the caspases-independent mitochondrial pathway in ASTC-a-1 cells
Med Oncol (2011) 28:307–314 DOI 10.1007/s12032-010-9431-5 Received: 15 December 2009 / Accepted: 14 January 2010 / Published online: 3 February 2010
