Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247 667, India.
Plant Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247 667, India.
Mol Biol Rep. 2020 Nov;47(11):8499-8511. doi: 10.1007/s11033-020-05892-8. Epub 2020 Oct 19.
Osteosarcoma is the most frequently occurring cancer in children as well as young adolescents and the metastatic forms worsen this condition to a further great extent. The metastatic dissemination of cancer cells is often acquired through a process of epithelial-mesenchymal transition (EMT). Since, phytochemicals have attracted intense interest in recent years due to their diverse pharmacological effects, in the present study, we investigated if berberine, a naturally occurring isoquinoline quaternary alkaloid, could modulate the EMT in osteosarcoma cells. Our experimental studies showed that berberine reduced cell viability, colony formation, wound healing ability and migration of osteosarcoma cells. Also, berberine significantly reduced the expression of matrix metalloproteinase (MMP)-2, suggesting its inhibitory action on the matrix metalloproteinases that are required for cancer cell invasion. The significant reduction in the expression of vimentin, N-cadherin, fibronectin and increased expression of E-cadherin further suggested its role in the inhibition of EMT in osteosarcoma cells. The downregulation of H3K27me3, as well as the decreased expression of the histone methyl transferase enzyme EZH2, further substantiated the fact that the plant alkaloid can be used as an epigenetic modulator in the treatment of osteosarcoma. In conclusion, our findings suggest that berberine inhibits proliferation and migration of osteosarcoma cells and most importantly reverses EMT along with modulation of key epigenetic regulators.
骨肉瘤是儿童和青少年中最常见的癌症，转移性形式使病情进一步恶化。癌细胞的转移扩散通常是通过上皮-间充质转化（EMT）过程获得的。由于植物化学物质因其多样化的药理作用而在近年来引起了强烈的兴趣，在本研究中，我们研究了小檗碱（一种天然存在的异喹啉季铵生物碱）是否可以调节骨肉瘤细胞中的 EMT。我们的实验研究表明，小檗碱降低了骨肉瘤细胞的活力、集落形成、伤口愈合能力和迁移能力。此外，小檗碱还显著降低了基质金属蛋白酶（MMP）-2 的表达，表明其对肿瘤细胞侵袭所需的基质金属蛋白酶具有抑制作用。波形蛋白、N-钙粘蛋白、纤连蛋白表达的显著减少和 E-钙粘蛋白表达的增加进一步表明其在抑制骨肉瘤细胞 EMT 中的作用。H3K27me3 的下调以及组蛋白甲基转移酶酶 EZH2 的表达减少进一步证实了植物生物碱可用作骨肉瘤治疗中的表观遗传调节剂。总之，我们的研究结果表明，小檗碱抑制骨肉瘤细胞的增殖和迁移，最重要的是，它可以逆转 EMT 并调节关键的表观遗传调节剂。
