期刊
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
卷 47, 期 1, 页码 1961-1970出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2019.1593854
关键词
Alantolactone; apoptosis; ROS; mitophagy; AKT
资金
- Scientific Research Program - Shaanxi Provincial Education Department [16JK1761]
- National Key Research and Development Program [2016YFC0905001]
- Hubei Natural Science Foundation [2018CFB464]
- Scientific Research Projects of Colleges and Universities in Gansu Province [2017A-146]
Alantolactone (Ala), a major sesquiterpene lactone extracted from Inula helenium, exerts potent anti-tumour activities in various cancers. However, the underlying mechanism of such activities is still ambiguous. This study focused on evaluating the anti-tumour effects and molecular mechanisms of Ala on HepG2 cells. Our results demonstrated that Ala might inhibit cellular proliferation, induce G2/M phase arrest and apoptosis in HepG2 cells. Specifically, this study confirmed that Ala induced G2/M phase arrest by upregulating p21, downregulating cyclin A1 and cyclin B1, and promoting cellular apoptosis by increasing the expression of cleaved caspase-3 and PARP. Furthermore, Ala caused an increase in reactive oxygen species (ROS) level and inhibition of ROS production significantly prevented Ala-induced apoptosis. Interestingly, the accumulation of ROS, in turn, suppressed the downstream AKT signalling. Finally, mitophagy of Ala-treated HepG2 cells was observed by Mito/Lyso staining. Mitophagy was significantly inhibited by downregulation of the expression of PINK1 and Parkin proteins. The inhibition of mitophagy by a mitophagy inhibitor was found to markedly enhance Ala-mediated apoptosis and growth inhibition in HepG2 cells. Consequently, Ala induced cellular apoptosis via ROS-mediated suppression of AKT signalling and inhibition of PINK1-mediated mitophagy. Thus, Ala has potential to be used for the treatment of liver cancer.
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