Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-12-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1593854 |
| Summary: | 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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| ISSN: | 2169-1401 2169-141X |