Glutathione transferase Pi (GSTP1) expression is increased in many cancer types and is associated with multidrug resistance and apoptosis inhibition. Inhibitors of GST P1-1 have the potential to overcome drug resistance and improve chemotherapy efficacy as adjuvant agents. This study investigated the effects of catechin and gossypol on human glutathione transferase Pi (GSTP1-1) activity and their cytotoxic effects on breast cancer cells (MCF-7) individually and in combination with tamoxifen. Gossypol effectively inhibited the enzyme with an IC50 value of 40 μM, compared to 200 μM for catechin. Gossypol showed stronger inhibition of GSTP1-1 activity (Ki = 63.3 ± 17.5 μM) compared to catechin (Ki = 220 ± 44 μM). Molecular docking analysis revealed their binding conformations to GSTP1-1, with gossypol binding at the subunit interface in an uncompetitive manner and catechin showing mixed non-competitive inhibition. Gossypol had severe cytotoxic effects on both MCF-7 cells and normal BJ1 cells, while catechin had a weak cytotoxic effect on MCF-7 cells only. Combination therapy with tamoxifen resulted in cytotoxicity of 27.3% and 35.2% when combined with catechin and gossypol, respectively. Gossypol showed higher toxicity to MCF-7 cells, but its strong effects on normal cells raised concerns about selectivity and potential side effects.

中文翻译：

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儿茶素和棉酚对人谷胱甘肽转移酶的抑制：通过动力学特性、分子对接及其对人 MCF-7 细胞活力的功效进行比较结构分析。

谷胱甘肽转移酶 Pi (GSTP1) 表达在许多癌症类型中增加，并且与多药耐药性和细胞凋亡抑制相关。GST P1-1 抑制剂作为辅助药物具有克服耐药性并提高化疗疗效的潜力。本研究调查了儿茶素和棉酚对人谷胱甘肽转移酶 Pi (GSTP1-1) 活性的影响，以及它们单独和与他莫昔芬联合使用对乳腺癌细胞 (MCF-7) 的细胞毒性作用。棉酚有效抑制该酶，IC50 值为 40 μM，而儿茶素的 IC50 值为 200 μM。与儿茶素 (Ki = 220 ± 44 μM) 相比，棉酚对 GSTP1-1 活性具有更强的抑制作用 (Ki = 63.3 ± 17.5 μM)。分子对接分析揭示了它们与 GSTP1-1 的结合构象，其中棉酚以非竞争性方式结合在亚基界面上，而儿茶素则显示出混合的非竞争性抑制。棉酚对MCF-7细胞和正常BJ1细胞均具有严重的细胞毒作用，而儿茶素仅对MCF-7细胞具有微弱的细胞毒作用。当与儿茶素和棉酚联合时，他莫昔芬联合治疗的细胞毒性分别为 27.3% 和 35.2%。棉酚对 MCF-7 细胞表现出较高的毒性，但其对正常细胞的强烈作用引起了人们对选择性和潜在副作用的担忧。