Potent antitumor activity of Laccaic acid and Phenethyl isothiocyanate combination in colorectal cancer via dual inhibition of DNA methyltransferase-1 and Histone deacetylase-1

Despite an incessant advancement in the treatment of Colorectal Cancer (CRC), 40% of individuals suffer from disease relapse which marks the need for new treatment options. In this study we report synergistic antitumor activity of Laccaic acid (LA) and Phenethyl isothiocyanate (PEITC) combination in colorectal Cancer via dual inhibition of DNA methyltransferase-1 and Histone deacetylase-1. Efficacy of combination was evaluated in both in-vitro and in-vivo experiments using human colon carcinoma cell line HT29 and 1,2-dimethyl hydrazine induced colon Cancer rat model, respectively. In the cell line studies treatment with combination showed reduced cell viability with apoptotic cell death compared to individual treatment groups which showed necrotic cell death. IC50 value for combination (0.478 μM) was much lower than LA (6.08 μM), PEITC (11.88 μM) and 5-Fluorouracil (9.88 μM). In the in-vivo study combination group significantly attenuated number of aberrant crypt foci, fecal consistency score, IL-6, TNF-α, DNMT1 and HDAC1 levels, histological findings and mortality as compared to negative control. Further, toxic effects produced by combination were significantly less. Results suggest potent synergistic efficacy of Laccaic acid and Phenethyl isothiocyanate combination in colorectal Cancer.

Colorectal cancer; DNA methyltransferase inhibitor 1; Epigenetic therapy; Histone methyltransferase inhibitor 1; Laccaic acid; Phenethyl isothiocyanate.