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 |
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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 |
| _version_ | 1818008691957301248 |
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| author | Xing Kang Hijuan Wang Yanwei Li Ying Xiao Lili Zhao Tingting Zhang Shaohe Zhou Xiaolun Zhou Yi Li Zhexing Shou Chao Chen Bin Li |
| author_facet | Xing Kang Hijuan Wang Yanwei Li Ying Xiao Lili Zhao Tingting Zhang Shaohe Zhou Xiaolun Zhou Yi Li Zhexing Shou Chao Chen Bin Li |
| author_sort | Xing Kang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T05:33:36Z |
| format | Article |
| id | doaj.art-1f85074b3e1a4b68861b7707bc711464 |
| institution | Directory Open Access Journal |
| issn | 2169-1401 2169-141X |
| language | English |
| last_indexed | 2024-04-14T05:33:36Z |
| publishDate | 2019-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj.art-1f85074b3e1a4b68861b7707bc7114642022-12-22T02:09:44ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014711961197010.1080/21691401.2019.1593854Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cellsXing Kang0Hijuan Wang1Yanwei Li2Ying Xiao3Lili Zhao4Tingting Zhang5Shaohe Zhou6Xiaolun Zhou7Yi Li8Zhexing Shou9Chao Chen10Bin Li11Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaDepartment of Pathogenic Biology, Gansu medical college, Pingliang, PR ChinaSchool of Computer Sciences, Xi’an Polytechnic University, Xi’an, PR ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR ChinaCollege of Life Science, National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi’an, PR ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR ChinaAlantolactone (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.https://www.tandfonline.com/doi/10.1080/21691401.2019.1593854AlantolactoneapoptosisROSmitophagyAKT |
| spellingShingle | Xing Kang Hijuan Wang Yanwei Li Ying Xiao Lili Zhao Tingting Zhang Shaohe Zhou Xiaolun Zhou Yi Li Zhexing Shou Chao Chen Bin Li Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells Artificial Cells, Nanomedicine, and Biotechnology Alantolactone apoptosis ROS mitophagy AKT |
| title | Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells |
| title_full | Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells |
| title_fullStr | Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells |
| title_full_unstemmed | Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells |
| title_short | Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells |
| title_sort | alantolactone induces apoptosis through ros mediated akt pathway and inhibition of pink1 mediated mitophagy in human hepg2 cells |
| topic | Alantolactone apoptosis ROS mitophagy AKT |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1593854 |
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