Anti-cancer activity and cellular uptake of 7,3′,4′- and 7,8,4′-trihydroxyisoflavone in HepG2 cells under hypoxic conditions

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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Bibliographic Details
Main Authors: Wen-Sheng Tzeng, Wei-Lin Teng, Pao-Hsien Huang, Feng-Lin Yen, Yow-Ling Shiue
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Cellular uptake
hepatocellular carcinoma
hypoxia
734′-trihydroxyisoflavone
784′-trihydroxyisoflavone
Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2023.2288806
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Summary: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.
ISSN:1475-6366
1475-6374

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