Curcumol Induces Apoptosis Via Caspases-independent Mitochondrial Pathway in Human Lung Adenocarcinoma ASTC-a-1 Cells
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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.
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Ma C, Tang X, Tang Q, Wang S, Zhang J, Lu Y Front Pharmacol. 2022; 13:1044115.
PMID: 36467048 PMC: 9716069. DOI: 10.3389/fphar.2022.1044115.
Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling.
Gao J, Hou D, Hu P, Mao G Transl Cancer Res. 2022; 10(5):2437-2450.
PMID: 35116559 PMC: 8798486. DOI: 10.21037/tcr-21-689.
Sheng W, Xu W, Ding J, Li L, You X, Wu Y Oncol Rep. 2021; 46(5).
PMID: 34590156 PMC: 8493056. DOI: 10.3892/or.2021.8197.
Wen T, Song L, Hua S Cancer Med. 2021; 10(7):2396-2422.
PMID: 33650320 PMC: 7982634. DOI: 10.1002/cam4.3660.