Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells.
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 G(2)/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 (∆Ψm), 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.
Zhang
Weiwei
W
MOE Key Libratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, 510631 Guangzhou, China.
Wang
Zhiping
Z
Chen
Tongsheng
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D012717:Sesquiterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D004365:Drugs, Chinese Herbal; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; C022801:curcumol; D020169:Caspases