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

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wen-Sheng Tzeng, Wei-Lin Teng, Pao-Hsien Huang, Feng-Lin Yen, Yow-Ling Shiue
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引用次数: 0

Abstract

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.

缺氧条件下 7,3',4'- 和 7,8,4'- 三羟基异黄酮在 HepG2 细胞中的抗癌活性和细胞吸收。
经动脉化疗栓塞术(TACE)用于治疗无法切除的肝细胞癌(HCC),但 TACE 引起的缺氧会导致预后不良。研究人员评估了大豆异黄酮的衍生物 7,3',4'-三羟基异黄酮(734THIF)和 7,8,4'-三羟基异黄酮(784THIF)在缺氧微环境下的抗癌作用。评估了这些异构体与环氧化酶-2(COX-2)和血管内皮生长因子受体 2(VEGFR2)的分子对接。在缺氧条件下,约 40 μM 的 734THIF 和 784THIF 对 HepG2 细胞增殖的抑制效果最佳。与 734THIF 相比,浓度为 40 μM 时,784THIF 能显著抑制缺氧前条件下 COX-2 的表达,抑制率为 67.73%。此外,40 μM 784THIF 还能下调缺氧、炎症和转移相关蛋白的表达,调节氧化应激,抑制抗凋亡蛋白的表达。HepG2对784THIF的吸收证实,在缺氧后或缺氧前条件下,784THIF水平较高,降解速度较慢。总之,我们的研究结果表明,与 734THIF 相比,784THIF 具有更好的抗癌效果和细胞吸收能力。
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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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