Cancer Research Lab., Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed to be University, Pune-Satara Road, Pune 411043, Maharashtra, India.
Department of Chemical Technology, University of Calcutta, 91 APC Road, Kolkata 700 009, India.
Biophys Chem. 2021 Jun;273:106588. doi: 10.1016/j.bpc.2021.106588. Epub 2021 Apr 2.
Histone deacetylase 8 (HDAC8) has emerged as a promising drug target for cancer therapeutics development. HDAC8 has been reported to regulate cancer cell proliferation, invasion and promote metastasis through modulation of cell cycle associated proteins. Of late, phytocompounds have been demonstrated to exhibit anticancer and anti-HDAC8 activity. Here, we have shown the HDAC8 inhibitory potential of an active phytocompound from HC9 (herbal composition-9), a polyherbal anticancer formulation based on the traditional Ayurvedic drug, Stanya Shodhan Kashaya. HC9 was recently reported to exhibit anticancer activity against breast cancer cells through induction of cell cycle arrest, decrease in migration and invasion as well as regulation of inflammation and chromatin modulators. In silico studies such as molecular docking, molecular dynamics (MD) simulation and binding free energy analyses showed greater binding energy values and interaction stability of MA with HDAC8 compared to other phytocompounds of HC9. Interestingly, in vitro validation confirmed the anti-HDAC8 activity of MA. Further, in vitro studies showed that MA significantly decreased the viability of breast and prostate cancer cell lines, thereby confirming its anticancer potential.
组蛋白去乙酰化酶 8（HDAC8）已成为癌症治疗药物开发的一个有前途的药物靶点。已有报道称，HDAC8 通过调节细胞周期相关蛋白来调节癌细胞的增殖、侵袭并促进转移。最近，植物化合物已被证明具有抗癌和抗 HDAC8 活性。在这里，我们展示了来自 HC9（草药组合物-9）的一种活性植物化合物的 HDAC8 抑制潜力，HC9 是一种基于传统阿育吠陀药物 Stanya Shodhan Kashaya 的多草药抗癌配方。HC9 最近被报道通过诱导细胞周期停滞、减少迁移和侵袭以及调节炎症和染色质调节剂来显示对乳腺癌细胞的抗癌活性。基于分子对接、分子动力学（MD）模拟和结合自由能分析等计算研究表明，与 HC9 的其他植物化合物相比，MA 与 HDAC8 的结合能值和相互作用稳定性更高。有趣的是，体外验证证实了 MA 的抗 HDAC8 活性。此外，体外研究表明 MA 显著降低了乳腺癌和前列腺癌细胞系的活力，从而证实了其抗癌潜力。
