Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells
Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the gr...
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MDPI AG
2020-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/7/1579 |
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| author | Haizhi Huang Allen Y. Chen Xingqian Ye Rongfa Guan Gary O. Rankin Yi Charlie Chen |
| author_facet | Haizhi Huang Allen Y. Chen Xingqian Ye Rongfa Guan Gary O. Rankin Yi Charlie Chen |
| author_sort | Haizhi Huang |
| collection | DOAJ |
| description | Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC<sub>50</sub> values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans. |
| first_indexed | 2024-03-10T20:48:02Z |
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| last_indexed | 2024-03-10T20:48:02Z |
| publishDate | 2020-03-01 |
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| spelling | doaj.art-98b1fc2424ef4854bde2c3d7f90f5dd32023-11-19T20:09:33ZengMDPI AGMolecules1420-30492020-03-01257157910.3390/molecules25071579Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer CellsHaizhi Huang0Allen Y. Chen1Xingqian Ye2Rongfa Guan3Gary O. Rankin4Yi Charlie Chen5College of Life Sciences, China Jiliang University, Hangzhou 310018, ChinaDepartment of Pharmacy Informatics, Seattle Children’s Hospital, Seattle, WA 98101, USACollege of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, ChinaCollege of Food Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, ChinaDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USACollege of Science, Technology & Mathematics, Alderson Broaddus University, Philippi, WV 26416, USAAmong women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC<sub>50</sub> values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.https://www.mdpi.com/1420-3049/25/7/1579apoptosisgalanginantioxidantsovarian cancerwestern blotflavonoid |
| spellingShingle | Haizhi Huang Allen Y. Chen Xingqian Ye Rongfa Guan Gary O. Rankin Yi Charlie Chen Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells Molecules apoptosis galangin antioxidants ovarian cancer western blot flavonoid |
| title | Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells |
| title_full | Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells |
| title_fullStr | Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells |
| title_full_unstemmed | Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells |
| title_short | Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells |
| title_sort | galangin a flavonoid from lesser galangal induced apoptosis via p53 dependent pathway in ovarian cancer cells |
| topic | apoptosis galangin antioxidants ovarian cancer western blot flavonoid |
| url | https://www.mdpi.com/1420-3049/25/7/1579 |
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