Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions
Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3′,4′-trihydroxyisoflavone (734THIF) and 7,8,4′-trihydroxyisoflavone (784T...
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2288806 |
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| author | Wen-Sheng Tzeng Wei-Lin Teng Pao-Hsien Huang Feng-Lin Yen Yow-Ling Shiue |
| author_facet | Wen-Sheng Tzeng Wei-Lin Teng Pao-Hsien Huang Feng-Lin Yen Yow-Ling Shiue |
| author_sort | Wen-Sheng Tzeng |
| collection | DOAJ |
| description | Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3′,4′-trihydroxyisoflavone (734THIF) and 7,8,4′-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 μM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 μM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 μM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF. |
| format | Article |
| id | doaj-art-27e17c9184d64324b3bfbef66f44967d |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-27e17c9184d64324b3bfbef66f44967d2024-12-26T09:30:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2023.2288806Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditionsWen-Sheng Tzeng0Wei-Lin Teng1Pao-Hsien Huang2Feng-Lin Yen3Yow-Ling Shiue4Department of Radiology, Pingtung Christian Hospital, Pingtung, TaiwanGraduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, TaiwanTransarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3′,4′-trihydroxyisoflavone (734THIF) and 7,8,4′-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 μM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 μM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 μM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF.https://www.tandfonline.com/doi/10.1080/14756366.2023.2288806Cellular uptakehepatocellular carcinomahypoxia734′-trihydroxyisoflavone784′-trihydroxyisoflavone |
| spellingShingle | Wen-Sheng Tzeng Wei-Lin Teng Pao-Hsien Huang Feng-Lin Yen Yow-Ling Shiue Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions Journal of Enzyme Inhibition and Medicinal Chemistry Cellular uptake hepatocellular carcinoma hypoxia 734′-trihydroxyisoflavone 784′-trihydroxyisoflavone |
| title | Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions |
| title_full | Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions |
| title_fullStr | Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions |
| title_full_unstemmed | Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions |
| title_short | Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions |
| title_sort | anti cancer activity and cellular uptake of 7 3 4 and 7 8 4 trihydroxyisoflavone in hepg2 cells under hypoxic conditions |
| topic | Cellular uptake hepatocellular carcinoma hypoxia 734′-trihydroxyisoflavone 784′-trihydroxyisoflavone |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2288806 |
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