Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells
Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from <i>Buxus microphylla</i>, was able to provoke mitophagy in lung cancer cells. CVB-D-induce...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5820 |
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| author | Cheng Zeng Tingting Zou Junyan Qu Xu Chen Suping Zhang Zhenghong Lin |
| author_facet | Cheng Zeng Tingting Zou Junyan Qu Xu Chen Suping Zhang Zhenghong Lin |
| author_sort | Cheng Zeng |
| collection | DOAJ |
| description | Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from <i>Buxus microphylla</i>, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patients |
| first_indexed | 2024-03-10T10:55:05Z |
| format | Article |
| id | doaj.art-e67ca3da887e4b2ea5e889d00cf81f79 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:55:05Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e67ca3da887e4b2ea5e889d00cf81f792023-11-21T21:58:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211582010.3390/ijms22115820Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer CellsCheng Zeng0Tingting Zou1Junyan Qu2Xu Chen3Suping Zhang4Zhenghong Lin5School of Life Sciences, Chongqing University, Chongqing 401331, ChinaSchool of Life Sciences, Chongqing University, Chongqing 401331, ChinaSchool of Life Sciences, Chongqing University, Chongqing 401331, ChinaSchool of Life Sciences, Chongqing University, Chongqing 401331, ChinaShenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Department of Pharmacology, Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518055, ChinaSchool of Life Sciences, Chongqing University, Chongqing 401331, ChinaMitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from <i>Buxus microphylla</i>, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patientshttps://www.mdpi.com/1422-0067/22/11/5820cyclovirobuxine DBNIP3mitophagyapoptosislung cancer |
| spellingShingle | Cheng Zeng Tingting Zou Junyan Qu Xu Chen Suping Zhang Zhenghong Lin Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells International Journal of Molecular Sciences cyclovirobuxine D BNIP3 mitophagy apoptosis lung cancer |
| title | Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells |
| title_full | Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells |
| title_fullStr | Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells |
| title_full_unstemmed | Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells |
| title_short | Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells |
| title_sort | cyclovirobuxine d induced mitophagy through the p65 bnip3 lc3 axis potentiates its apoptosis inducing effects in lung cancer cells |
| topic | cyclovirobuxine D BNIP3 mitophagy apoptosis lung cancer |
| url | https://www.mdpi.com/1422-0067/22/11/5820 |
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