Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage
Norcantharidin (NCTD), a cantharidin derivative, induces ROS generation and is widely used to treat CRC. In this study, we clarified the role and mechanism of action of norcantharidin in increasing CRC sensitivity to radiotherapy. We treated the CRC cell lines LoVo and DLD-1 with NCTD (10 or 50 μmol...
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MDPI AG
2024-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/3/347 |
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| author | Qiong Xu Heng Zhang Haoren Qin Huaqing Wang Hui Wang |
| author_facet | Qiong Xu Heng Zhang Haoren Qin Huaqing Wang Hui Wang |
| author_sort | Qiong Xu |
| collection | DOAJ |
| description | Norcantharidin (NCTD), a cantharidin derivative, induces ROS generation and is widely used to treat CRC. In this study, we clarified the role and mechanism of action of norcantharidin in increasing CRC sensitivity to radiotherapy. We treated the CRC cell lines LoVo and DLD-1 with NCTD (10 or 50 μmol/L), ionizing radiation (IR, 6 Gy), and a combination of the two and found that NCTD significantly inhibited the proliferation of CRC cells and enhanced their sensitivity to radiotherapy. NCTD induced ROS generation by decreasing the mitochondrial membrane potential, increasing mitochondrial membrane permeability, and promoting cytochrome C release from mitochondria into the cytoplasm. IR combined with NCTD induced ROS production, which activated the mitochondrial fission protein DRP1, leading to increased mitochondrial fission and CRC sensitivity to radiotherapy. NCTD also reduced CRC cell resistance to radiotherapy by blocking the cell cycle at the G2/M phase and decreasing p-CHK2, cyclin B1, and p-CDC2 expression. NCTD and IR also inhibited radiation resistance by causing DNA damage. Our findings provide evidence for the potential therapeutic use of NCTD and IR against CRC. Moreover, this study elucidates whether NCTD can overcome CRC radiation tolerance and provides insights into the underlying mechanisms. |
| first_indexed | 2024-04-24T18:36:48Z |
| format | Article |
| id | doaj.art-82caf80833b4478cb5f31cbbcf44c081 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-04-24T18:36:48Z |
| publishDate | 2024-03-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-82caf80833b4478cb5f31cbbcf44c0812024-03-27T13:18:39ZengMDPI AGAntioxidants2076-39212024-03-0113334710.3390/antiox13030347Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial DamageQiong Xu0Heng Zhang1Haoren Qin2Huaqing Wang3Hui Wang4Department of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300350, ChinaDepartment of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300350, ChinaSchool of Medicine, Nankai University, Tianjin 300350, ChinaDepartment of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300350, ChinaDepartment of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300350, ChinaNorcantharidin (NCTD), a cantharidin derivative, induces ROS generation and is widely used to treat CRC. In this study, we clarified the role and mechanism of action of norcantharidin in increasing CRC sensitivity to radiotherapy. We treated the CRC cell lines LoVo and DLD-1 with NCTD (10 or 50 μmol/L), ionizing radiation (IR, 6 Gy), and a combination of the two and found that NCTD significantly inhibited the proliferation of CRC cells and enhanced their sensitivity to radiotherapy. NCTD induced ROS generation by decreasing the mitochondrial membrane potential, increasing mitochondrial membrane permeability, and promoting cytochrome C release from mitochondria into the cytoplasm. IR combined with NCTD induced ROS production, which activated the mitochondrial fission protein DRP1, leading to increased mitochondrial fission and CRC sensitivity to radiotherapy. NCTD also reduced CRC cell resistance to radiotherapy by blocking the cell cycle at the G2/M phase and decreasing p-CHK2, cyclin B1, and p-CDC2 expression. NCTD and IR also inhibited radiation resistance by causing DNA damage. Our findings provide evidence for the potential therapeutic use of NCTD and IR against CRC. Moreover, this study elucidates whether NCTD can overcome CRC radiation tolerance and provides insights into the underlying mechanisms.https://www.mdpi.com/2076-3921/13/3/347ROSNCTDcolorectal cancermitochondriaDRP1 |
| spellingShingle | Qiong Xu Heng Zhang Haoren Qin Huaqing Wang Hui Wang Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage Antioxidants ROS NCTD colorectal cancer mitochondria DRP1 |
| title | Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage |
| title_full | Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage |
| title_fullStr | Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage |
| title_full_unstemmed | Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage |
| title_short | Norcantharidin Sensitizes Colorectal Cancer Cells to Radiotherapy via Reactive Oxygen Species–DRP1-Mediated Mitochondrial Damage |
| title_sort | norcantharidin sensitizes colorectal cancer cells to radiotherapy via reactive oxygen species drp1 mediated mitochondrial damage |
| topic | ROS NCTD colorectal cancer mitochondria DRP1 |
| url | https://www.mdpi.com/2076-3921/13/3/347 |
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