Berberine reverses epithelial-mesenchymal transition and modulates histone methylation in osteosarcoma cells
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ORIGINAL ARTICLE
Berberine reverses epithelial‑mesenchymal transition and modulates histone methylation in osteosarcoma cells Rutusmita Mishra1 · Sandip Nathani1 · Ritu Varshney1 · Debabrata Sircar2 · Partha Roy1 Received: 16 June 2020 / Accepted: 3 October 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Berberine · Osteosarcoma · Epithelial-mesenchymal transition · Epigenetic · Histone methylation
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05892-8) contains supplementary material, which is available to authorized users. * Partha Roy [email protected] Rutusmita Mishra [email protected] Sandip Nathani [email protected] Ritu Varshney [email protected] Debabrata Sircar [email protected] 1
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
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Osteosarcoma is defined as the primary cancer of bone, most prominently occurring in the metaphysis of long bones of children, young adolescents (≤ 24 years) and later stage of elderly people with an increased bone turnover [1]. Although localized osteosarcoma incidence shows a 5-year survival rate in almost 70% of the cases but the metastatic form worsens this condition [2]. Metastatic form of osteosarcoma r
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