Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor‐beta (TGF‐β) signaling pathway, pivotal in breast cancer, is a promising approach. TGF‐β inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation. This study explores naturally occurring flavonoids' interactions with TGF‐β. Using molecular docking against the protein's crystal structure (PDB Id: 1PY5), Gossypin showed the highest docking score and underwent molecular dynamics simulation, revealing complex flexibility and explaining how flavonoids impede TGF‐β signaling in breast cancer. ADMET predictions adhered to Lipinski’s rule of Five. Insights into flavonoid‐TGF‐β binding offer a novel angle for breast cancer treatment. Flavonoids having a good docking score like gossypin, morin, luteolin and taxifolin shown potent cytotoxic effect on breast cancer cell line, MCF‐7. Understanding these interactions could inspire flavonoid‐based therapies targeting TGF‐β to halt breast cancer growth. These findings pave the way for personalized, targeted breast cancer therapies, offering hope against this formidable disease.

中文翻译：

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天然存在的黄酮类化合物作为乳腺癌 TGF-β 抑制剂的计算探索：来自对接和分子动力学模拟以及体外细胞毒性研究的见解

乳腺癌是一个全球性的健康问题，需要创新的治疗方法。针对乳腺癌中至关重要的转化生长因子-β (TGF-β) 信号通路是一种很有前途的方法。 TGF-β 通过 G1 期细胞周期停滞来抑制增殖，最初充当抑制剂，但在后期，它通过增强运动性、侵袭性和转移形成来促进进展。本研究探讨了天然存在的类黄酮与 TGF-β 的相互作用。通过针对蛋白质晶体结构（PDB Id：1PY5）的分子对接，Gossypin 显示了最高的对接分数，并进行了分子动力学模拟，揭示了复杂的灵活性并解释了黄酮类化合物如何阻碍乳腺癌中的 TGF-β 信号传导。 ADMET 预测遵循利平斯基五法则。对类黄酮-TGF-β结合的深入了解为乳腺癌治疗提供了一个新的角度。具有良好对接分数的黄酮类化合物，如棉酚、桑色素、木犀草素和花旗松素，对乳腺癌细胞系 MCF-7 表现出有效的细胞毒性作用。了解这些相互作用可以激发针对 TGF-β 的类黄酮疗法来阻止乳腺癌生长。这些发现为个性化、靶向乳腺癌治疗铺平了道路，为对抗这种可怕的疾病带来了希望。