Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy
Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of <i>Garcinia nujiangensis</i>, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G<sub>0/1</sub> arrest and apoptosis, t...
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MDPI AG
2021-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/10/2858 |
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| author | Jiling Feng Anahitasadat Mansouripour Zhichao Xi Li Zhang Gang Xu Hua Zhou Hongxi Xu |
| author_facet | Jiling Feng Anahitasadat Mansouripour Zhichao Xi Li Zhang Gang Xu Hua Zhou Hongxi Xu |
| author_sort | Jiling Feng |
| collection | DOAJ |
| description | Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of <i>Garcinia nujiangensis</i>, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G<sub>0/1</sub> arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs. |
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| format | Article |
| id | doaj.art-573a07c3f20e4f678a83559aaac2d06c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:30:36Z |
| publishDate | 2021-05-01 |
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| spelling | doaj.art-573a07c3f20e4f678a83559aaac2d06c2023-11-21T19:18:11ZengMDPI AGMolecules1420-30492021-05-012610285810.3390/molecules26102858Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting MitophagyJiling Feng0Anahitasadat Mansouripour1Zhichao Xi2Li Zhang3Gang Xu4Hua Zhou5Hongxi Xu6Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaInstitute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai 201203, ChinaInstitute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai 201203, ChinaNujiangexanthone A (NJXA), a bioactive component isolated from the leaves of <i>Garcinia nujiangensis</i>, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G<sub>0/1</sub> arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs.https://www.mdpi.com/1420-3049/26/10/2858nujiangexanthone AmitophagyATG7starvation |
| spellingShingle | Jiling Feng Anahitasadat Mansouripour Zhichao Xi Li Zhang Gang Xu Hua Zhou Hongxi Xu Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy Molecules nujiangexanthone A mitophagy ATG7 starvation |
| title | Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy |
| title_full | Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy |
| title_fullStr | Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy |
| title_full_unstemmed | Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy |
| title_short | Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy |
| title_sort | nujiangexanthone a inhibits cervical cancer cell proliferation by promoting mitophagy |
| topic | nujiangexanthone A mitophagy ATG7 starvation |
| url | https://www.mdpi.com/1420-3049/26/10/2858 |
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