Repurposing of sodium valproate in colon cancer associated with diabetes mellitus: Role of HDAC inhibition

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Mayur M Patel, Bhoomika M Patel

Abstract

Diabetic patients are at greater risk for colon cancer. Histone deacetylases (HDACs) serve as common target for both. The key objective of the study was to evaluate the effect of sodium valproate in type 2 diabetes mellitus associated colon cancer. High fat diet and streptozotocin were used to induce type 2 diabetes. Following this, after diabetes confirmation, colon cancer was induced using 1,2 dimethylhydrazine (25 mg/kg, s.c.) once weekly from 7th week to 20th weeks. Sodium valproate (200 mg/kg) treatment was given from 20th to 24th week. At the end of 24 weeks, several enzymatic and biochemical parameters, were estimated. MTT, clonogenic and scratch wound healing assay were carried out in HCT-15 cell line. Hyperglycemia, hyperinsulinemia, increase in cytokines (TNF-α and IL-1β) and carcinoembryonic antigen and presence of proliferating cells was seen in disease control animals which was prevented by sodium valproate treatment. Overexpression of relative HDAC2 mRNA levels was found in diseased control animals, which was reduced by sodium valproate treatment. IC50 of sodium valproate was found to be 3.40 mM and 3.73 mM at 48 h and 72 h respectively on HCT-15 cell line. Sodium valproate also dose dependently prevented colony f...Continue Reading

Citations

Jun 20, 2019·International Journal of Molecular Sciences·Celeste CocoMonica Montagnani
Jan 29, 2019·Current Topics in Medicinal Chemistry·Yu BaiGuihua Cui
Dec 29, 2020·European Journal of Pharmacology·Saumitra Gajjar, Bhoomika M Patel
Feb 12, 2021·Expert Opinion on Drug Delivery·Preksha Vinchhi, Mayur M Patel
Dec 15, 2020·Frontiers in Oncology·Michel Montalvo-CasimiroLuis A Herrera
Jan 16, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Yiming ChenLei Zhang
Mar 15, 2021·European Journal of Medicinal Chemistry·Piyush GediyaManjunath D Ghate
Jun 24, 2021·Current Pharmaceutical Design·Pallavi Kumari, Shweta Dang

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