High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway
Abstract Background Mitochondrial dysfunction is closely associated with cancer development. Colorectal cancer (CRC) cells often exhibit altered energy metabolism, characterized by increased glycolysis and reduced oxidative phosphorylation. Enhancing mitochondrial biogenesis and function may represe...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-025-06211-z |
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| _version_ | 1849691588131815424 |
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| author | RuiYang Hong Su Min Jia Huang Mou Zou DongYu Zhou Yun Liang |
| author_facet | RuiYang Hong Su Min Jia Huang Mou Zou DongYu Zhou Yun Liang |
| author_sort | RuiYang Hong |
| collection | DOAJ |
| description | Abstract Background Mitochondrial dysfunction is closely associated with cancer development. Colorectal cancer (CRC) cells often exhibit altered energy metabolism, characterized by increased glycolysis and reduced oxidative phosphorylation. Enhancing mitochondrial biogenesis and function may represent a promising therapeutic approach. High-dose vitamin C has demonstrated anti-tumor properties and the ability to reverse the Warburg effect, but its role in regulating mitochondrial biogenesis and function remains unclear. Methods We evaluated the altered mitochondrial functional status of HCT116 colorectal cancer cells compared to FHC colorectal epithelial cells, assessed the effects of high-dose vitamin C on mitochondrial biogenesis and function in HCT116 cells, and explored the underlying regulatory mechanisms. Results HCT116 cells exhibited mitochondrial dysfunction compared to FHC cells, including decreased expression of electron transport chain complexes III and IV, reduced TFAM levels, and lower mtDNA content. Vitamin C treatment significantly enhanced mitochondrial biogenesis and function, as reflected by increased AMPK phosphorylation, upregulation of PGC-1α, SOD2, NRF2, TFAM, MT-CYB, and MTCO1, elevated mtDNA content, restored membrane potential, enhanced oxidative phosphorylation, and reduced glycolytic activity. Furthermore, vitamin C markedly suppressed HCT116 cell viability and clonogenic capacity, while these effects were substantially diminished by cotreatment with Compound C. Conclusion This study demonstrates that high-dose vitamin C ameliorates mitochondrial dysfunction and promotes mitochondrial biogenesis and function in colorectal cancer cells through activation of the AMPK–PGC-1α signaling pathway, thereby suppressing tumor cell proliferation. These findings suggest that vitamin C may serve as a promising therapeutic agent for targeting mitochondrial metabolism in colorectal cancer. |
| format | Article |
| id | doaj-art-09e50f6ab4d34b3cb93cc4e9df469dac |
| institution | DOAJ |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-09e50f6ab4d34b3cb93cc4e9df469dac2025-08-20T03:20:59ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-05-01151511310.1007/s00432-025-06211-zHigh-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathwayRuiYang Hong0Su Min1Jia Huang2Mou Zou3DongYu Zhou4Yun Liang5The First Affiliated Hospital of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Mitochondrial dysfunction is closely associated with cancer development. Colorectal cancer (CRC) cells often exhibit altered energy metabolism, characterized by increased glycolysis and reduced oxidative phosphorylation. Enhancing mitochondrial biogenesis and function may represent a promising therapeutic approach. High-dose vitamin C has demonstrated anti-tumor properties and the ability to reverse the Warburg effect, but its role in regulating mitochondrial biogenesis and function remains unclear. Methods We evaluated the altered mitochondrial functional status of HCT116 colorectal cancer cells compared to FHC colorectal epithelial cells, assessed the effects of high-dose vitamin C on mitochondrial biogenesis and function in HCT116 cells, and explored the underlying regulatory mechanisms. Results HCT116 cells exhibited mitochondrial dysfunction compared to FHC cells, including decreased expression of electron transport chain complexes III and IV, reduced TFAM levels, and lower mtDNA content. Vitamin C treatment significantly enhanced mitochondrial biogenesis and function, as reflected by increased AMPK phosphorylation, upregulation of PGC-1α, SOD2, NRF2, TFAM, MT-CYB, and MTCO1, elevated mtDNA content, restored membrane potential, enhanced oxidative phosphorylation, and reduced glycolytic activity. Furthermore, vitamin C markedly suppressed HCT116 cell viability and clonogenic capacity, while these effects were substantially diminished by cotreatment with Compound C. Conclusion This study demonstrates that high-dose vitamin C ameliorates mitochondrial dysfunction and promotes mitochondrial biogenesis and function in colorectal cancer cells through activation of the AMPK–PGC-1α signaling pathway, thereby suppressing tumor cell proliferation. These findings suggest that vitamin C may serve as a promising therapeutic agent for targeting mitochondrial metabolism in colorectal cancer.https://doi.org/10.1007/s00432-025-06211-zVitamin CColorectal cancerMitochondrial biogenesisAMPKPGC-1α |
| spellingShingle | RuiYang Hong Su Min Jia Huang Mou Zou DongYu Zhou Yun Liang High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway Journal of Cancer Research and Clinical Oncology Vitamin C Colorectal cancer Mitochondrial biogenesis AMPK PGC-1α |
| title | High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway |
| title_full | High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway |
| title_fullStr | High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway |
| title_full_unstemmed | High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway |
| title_short | High-dose vitamin C promotes mitochondrial biogenesis in HCT116 colorectal cancer cells by regulating the AMPK/PGC-1α signaling pathway |
| title_sort | high dose vitamin c promotes mitochondrial biogenesis in hct116 colorectal cancer cells by regulating the ampk pgc 1α signaling pathway |
| topic | Vitamin C Colorectal cancer Mitochondrial biogenesis AMPK PGC-1α |
| url | https://doi.org/10.1007/s00432-025-06211-z |
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