Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways
Abstract Background Gastric cancer (GC) is one of the most prevalent cancers and the fifth leading cause of cancer-related deaths globally. Methyl mycophenolate (MMP), a methyl ester derivative of mycophenolic acid, is derived from the marine fungus Phaeosphaeria spartinae, yet its role in GC remain...
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BMC
2025-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03835-6 |
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| author | Xiaofang Liu Ning Xu Jie Wang Kaining Chen Huiwen Ke Yufen Xu Dianying Feng Lishi Xiao Xiangqi Meng Shi Chen Hongyan Yu |
| author_facet | Xiaofang Liu Ning Xu Jie Wang Kaining Chen Huiwen Ke Yufen Xu Dianying Feng Lishi Xiao Xiangqi Meng Shi Chen Hongyan Yu |
| author_sort | Xiaofang Liu |
| collection | DOAJ |
| description | Abstract Background Gastric cancer (GC) is one of the most prevalent cancers and the fifth leading cause of cancer-related deaths globally. Methyl mycophenolate (MMP), a methyl ester derivative of mycophenolic acid, is derived from the marine fungus Phaeosphaeria spartinae, yet its role in GC remains unexplored. Purpose This study aims to investigate the therapeutic potential of MMP in GC and elucidate its underlying mechanisms. Methods We screened marine compounds for their inhibitory activity against GC cells using cell viability, colony formation assays, cell cycle analysis, and apoptosis detection. RNA sequencing and KEGG enrichment analysis identified key downstream pathways activated by MMP. Western blotting, qRT-PCR, and immunohistochemistry confirmed changes in the p53 signaling pathway. Protein stability was assessed through turnover and ubiquitination assays, while Co-IP verified the effect of MMP on p53 binding to MDM2. An in vivo tumorigenesis study evaluated MMP’s efficacy and safety in mice. Results MMP significantly inhibited GC cell proliferation and colony formation, induced apoptosis through the caspase pathway, and caused cell cycle G1 arrest by downregulating CDK4, CDK2 and upregulating p27. Mechanistically, MMP increased p53 protein levels and activated downstream targets (p21, PUMA, GADD45A) in a dose-dependent manner. It enhanced p53 stability by reducing ubiquitination. MMP injection in mice significantly inhibited tumor growth in a subcutaneous xenograft model. Conclusion MMP displays anti-GC activity by inducing apoptosis and cell cycle arrest via the p53 pathway. Our findings suggest MMP’s potential as a therapeutic agent for GC intervention. |
| format | Article |
| id | doaj-art-e45d2534a40e450eba75f48ab1667c68 |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-e45d2534a40e450eba75f48ab1667c682025-08-20T03:21:02ZengBMCCancer Cell International1475-28672025-06-0125111710.1186/s12935-025-03835-6Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathwaysXiaofang Liu0Ning Xu1Jie Wang2Kaining Chen3Huiwen Ke4Yufen Xu5Dianying Feng6Lishi Xiao7Xiangqi Meng8Shi Chen9Hongyan Yu10Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese MedicineDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese MedicineDepartment of Radiation Oncology, Dalian Municipal Central HospitalDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese MedicineDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen UniversityDepartment of General Surgery, Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract Background Gastric cancer (GC) is one of the most prevalent cancers and the fifth leading cause of cancer-related deaths globally. Methyl mycophenolate (MMP), a methyl ester derivative of mycophenolic acid, is derived from the marine fungus Phaeosphaeria spartinae, yet its role in GC remains unexplored. Purpose This study aims to investigate the therapeutic potential of MMP in GC and elucidate its underlying mechanisms. Methods We screened marine compounds for their inhibitory activity against GC cells using cell viability, colony formation assays, cell cycle analysis, and apoptosis detection. RNA sequencing and KEGG enrichment analysis identified key downstream pathways activated by MMP. Western blotting, qRT-PCR, and immunohistochemistry confirmed changes in the p53 signaling pathway. Protein stability was assessed through turnover and ubiquitination assays, while Co-IP verified the effect of MMP on p53 binding to MDM2. An in vivo tumorigenesis study evaluated MMP’s efficacy and safety in mice. Results MMP significantly inhibited GC cell proliferation and colony formation, induced apoptosis through the caspase pathway, and caused cell cycle G1 arrest by downregulating CDK4, CDK2 and upregulating p27. Mechanistically, MMP increased p53 protein levels and activated downstream targets (p21, PUMA, GADD45A) in a dose-dependent manner. It enhanced p53 stability by reducing ubiquitination. MMP injection in mice significantly inhibited tumor growth in a subcutaneous xenograft model. Conclusion MMP displays anti-GC activity by inducing apoptosis and cell cycle arrest via the p53 pathway. Our findings suggest MMP’s potential as a therapeutic agent for GC intervention.https://doi.org/10.1186/s12935-025-03835-6Gastric cancerNatural marine compoundsMethyl mycophenolatep53Ubiquitination |
| spellingShingle | Xiaofang Liu Ning Xu Jie Wang Kaining Chen Huiwen Ke Yufen Xu Dianying Feng Lishi Xiao Xiangqi Meng Shi Chen Hongyan Yu Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways Cancer Cell International Gastric cancer Natural marine compounds Methyl mycophenolate p53 Ubiquitination |
| title | Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| title_full | Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| title_fullStr | Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| title_full_unstemmed | Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| title_short | Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| title_sort | marine natural product methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways |
| topic | Gastric cancer Natural marine compounds Methyl mycophenolate p53 Ubiquitination |
| url | https://doi.org/10.1186/s12935-025-03835-6 |
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