Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling
Objective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1338260/full |
| _version_ | 1797362386292703232 |
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| author | Yanan Wang Yanan Wang Qingmin He Kang Rong Kang Rong Mingyang Zhu Mingyang Zhu Xiaoxiao Zhao Pengyuan Zheng Pengyuan Zheng Pengyuan Zheng Yang Mi Yang Mi Yang Mi |
| author_facet | Yanan Wang Yanan Wang Qingmin He Kang Rong Kang Rong Mingyang Zhu Mingyang Zhu Xiaoxiao Zhao Pengyuan Zheng Pengyuan Zheng Pengyuan Zheng Yang Mi Yang Mi Yang Mi |
| author_sort | Yanan Wang |
| collection | DOAJ |
| description | Objective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying the effects of vitamin D3 on tumors is not fully understood. Here, we used network pharmacology and in vitro experimental approaches to explore the mechanism of vitamin D3 activity in the context of gastric cancer.Methods: The Targetnet, SuperPred, SwissTargetPrediction, and PharmMapper databases were screened for potential drug-related targets, while we used data from the PharmGKB, Drugbank, OMIM, DisGeNET, CTD, and GeneCards databases to identify potential targets associated with gastric cancer. Disease-drug crossover genes were obtained by constructing Venn diagrams. Gene ontology and Kyoto Encyclopedia of Genomes (KEGG) enrichment analyses of crossover genes were conducted and STRING was used to generate protein interaction networks and identify core targets. CCK-8 experiments were performed and apoptosis detected to assess the effect of vitamin D3 on gastric cancer cells. Western blotting was applied to detect p53/AMPK/mTOR signaling, as well as autophagy-, cell cycle-, and apoptosis-related proteins.Results: A total of 485 targets of vitamin D3 activity were obtained and 1200 gastric cancer disease-related targets discovered. Further, 60 potential targets for vitamin D3 in gastric cancer treatment were identified. KEGG analysis indicated that potential targets were mainly involved in the cell cycle, HIF-1 signaling, and the AMPK pathway, among other pathways. These findings were validated using cellular experiments, which demonstrated that the viability of AGS and SGC-7901 cells was impeded by vitamin D3. Further, vitamin D3 promoted apoptosis and inhibited the cell cycle in those cell lines, as well as activating the p53/AMPK/mTOR pathway, which promotes autophagy and inhibits tumor development.Conclusion: Our network pharmacological analyses provide preliminarily data supporting a role for vitamin D3 in promoting autophagy and apoptosis in gastric cancer cells, and in activating the p53/AMPK/mTOR pathway, which inhibits gastric cancer cell proliferation. Our findings demonstrate the molecular mechanism underlying the effect of vitamin D3 in cure of gastric cancer. |
| first_indexed | 2024-03-08T16:06:19Z |
| format | Article |
| id | doaj.art-464859a4da374c9ba3e89a6c249d1a66 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T16:06:19Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-464859a4da374c9ba3e89a6c249d1a662024-01-08T05:12:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.13382601338260Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signalingYanan Wang0Yanan Wang1Qingmin He2Kang Rong3Kang Rong4Mingyang Zhu5Mingyang Zhu6Xiaoxiao Zhao7Pengyuan Zheng8Pengyuan Zheng9Pengyuan Zheng10Yang Mi11Yang Mi12Yang Mi13Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaAcademy of Medical Science, Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi, ChinaHenan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaAcademy of Medical Science, Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaAcademy of Medical Science, Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaObjective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying the effects of vitamin D3 on tumors is not fully understood. Here, we used network pharmacology and in vitro experimental approaches to explore the mechanism of vitamin D3 activity in the context of gastric cancer.Methods: The Targetnet, SuperPred, SwissTargetPrediction, and PharmMapper databases were screened for potential drug-related targets, while we used data from the PharmGKB, Drugbank, OMIM, DisGeNET, CTD, and GeneCards databases to identify potential targets associated with gastric cancer. Disease-drug crossover genes were obtained by constructing Venn diagrams. Gene ontology and Kyoto Encyclopedia of Genomes (KEGG) enrichment analyses of crossover genes were conducted and STRING was used to generate protein interaction networks and identify core targets. CCK-8 experiments were performed and apoptosis detected to assess the effect of vitamin D3 on gastric cancer cells. Western blotting was applied to detect p53/AMPK/mTOR signaling, as well as autophagy-, cell cycle-, and apoptosis-related proteins.Results: A total of 485 targets of vitamin D3 activity were obtained and 1200 gastric cancer disease-related targets discovered. Further, 60 potential targets for vitamin D3 in gastric cancer treatment were identified. KEGG analysis indicated that potential targets were mainly involved in the cell cycle, HIF-1 signaling, and the AMPK pathway, among other pathways. These findings were validated using cellular experiments, which demonstrated that the viability of AGS and SGC-7901 cells was impeded by vitamin D3. Further, vitamin D3 promoted apoptosis and inhibited the cell cycle in those cell lines, as well as activating the p53/AMPK/mTOR pathway, which promotes autophagy and inhibits tumor development.Conclusion: Our network pharmacological analyses provide preliminarily data supporting a role for vitamin D3 in promoting autophagy and apoptosis in gastric cancer cells, and in activating the p53/AMPK/mTOR pathway, which inhibits gastric cancer cell proliferation. Our findings demonstrate the molecular mechanism underlying the effect of vitamin D3 in cure of gastric cancer.https://www.frontiersin.org/articles/10.3389/fphar.2023.1338260/fullnetwork pharmacologymolecular dockingvitamin D3gastric cancermolecular mechanismautophagy |
| spellingShingle | Yanan Wang Yanan Wang Qingmin He Kang Rong Kang Rong Mingyang Zhu Mingyang Zhu Xiaoxiao Zhao Pengyuan Zheng Pengyuan Zheng Pengyuan Zheng Yang Mi Yang Mi Yang Mi Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling Frontiers in Pharmacology network pharmacology molecular docking vitamin D3 gastric cancer molecular mechanism autophagy |
| title | Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling |
| title_full | Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling |
| title_fullStr | Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling |
| title_full_unstemmed | Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling |
| title_short | Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling |
| title_sort | vitamin d3 promotes gastric cancer cell autophagy by mediating p53 ampk mtor signaling |
| topic | network pharmacology molecular docking vitamin D3 gastric cancer molecular mechanism autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1338260/full |
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