Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme
Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to the absence of specific targeted treatments. In this study, we explored the therapeutic potential of xanthocillin X dimethyl ether (XanDME), a naturally occurring isocyanide isolated from the marine fungus <i...
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MDPI AG
2025-03-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/4/146 |
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| author | Jingjing Du Xuening Zhang Kaiqiang Guo Wanjun Lin Wenjian Lan Zi Wang Meina Shi Zifeng Huang Houjin Li Wenzhe Ma |
| author_facet | Jingjing Du Xuening Zhang Kaiqiang Guo Wanjun Lin Wenjian Lan Zi Wang Meina Shi Zifeng Huang Houjin Li Wenzhe Ma |
| author_sort | Jingjing Du |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to the absence of specific targeted treatments. In this study, we explored the therapeutic potential of xanthocillin X dimethyl ether (XanDME), a naturally occurring isocyanide isolated from the marine fungus <i>Scedosporium apiospermum</i>, on TNBC. To elucidate the underlying mechanism, we initially demonstrated that XanDME directly binds to hemin, the oxidized form of heme, in vitro, corroborating previous reports. This interaction led to the depletion of intracellular regulatory heme. We further established that XanDME translocates into the mitochondria, where it interacts with crucial hemoproteins, namely cytochromes. The binding of XanDME with mitochondrial cytochromes disrupts the electron transport chain (ETC), inhibits the activity of mitochondrial complexes, and inactivates mitochondrial respiration. The inhibitory activity of XanDME on mitochondrial function significantly contributes to its anti-TNBC effects, as observed both in vitro and in vivo. Our study underscores the potential of XanDME against TNBC, warranting further investigations. |
| format | Article |
| id | doaj-art-3f27d0a0c4ce48b4944a86ce25466fce |
| institution | OA Journals |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-3f27d0a0c4ce48b4944a86ce25466fce2025-08-20T02:28:37ZengMDPI AGMarine Drugs1660-33972025-03-0123414610.3390/md23040146Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial HemeJingjing Du0Xuening Zhang1Kaiqiang Guo2Wanjun Lin3Wenjian Lan4Zi Wang5Meina Shi6Zifeng Huang7Houjin Li8Wenzhe Ma9School of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaSchool of Chemistry, Sun Yat-Sen University, Guangzhou 510006, ChinaSchool of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, ChinaTriple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to the absence of specific targeted treatments. In this study, we explored the therapeutic potential of xanthocillin X dimethyl ether (XanDME), a naturally occurring isocyanide isolated from the marine fungus <i>Scedosporium apiospermum</i>, on TNBC. To elucidate the underlying mechanism, we initially demonstrated that XanDME directly binds to hemin, the oxidized form of heme, in vitro, corroborating previous reports. This interaction led to the depletion of intracellular regulatory heme. We further established that XanDME translocates into the mitochondria, where it interacts with crucial hemoproteins, namely cytochromes. The binding of XanDME with mitochondrial cytochromes disrupts the electron transport chain (ETC), inhibits the activity of mitochondrial complexes, and inactivates mitochondrial respiration. The inhibitory activity of XanDME on mitochondrial function significantly contributes to its anti-TNBC effects, as observed both in vitro and in vivo. Our study underscores the potential of XanDME against TNBC, warranting further investigations.https://www.mdpi.com/1660-3397/23/4/146xanthocillin X dimethyl ethertriple-negative breast cancerhememitochondria |
| spellingShingle | Jingjing Du Xuening Zhang Kaiqiang Guo Wanjun Lin Wenjian Lan Zi Wang Meina Shi Zifeng Huang Houjin Li Wenzhe Ma Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme Marine Drugs xanthocillin X dimethyl ether triple-negative breast cancer heme mitochondria |
| title | Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme |
| title_full | Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme |
| title_fullStr | Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme |
| title_full_unstemmed | Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme |
| title_short | Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme |
| title_sort | xanthocillin x dimethyl ether exhibits anti proliferative effect on triple negative breast cancer by depletion of mitochondrial heme |
| topic | xanthocillin X dimethyl ether triple-negative breast cancer heme mitochondria |
| url | https://www.mdpi.com/1660-3397/23/4/146 |
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