Determination of cytotoxic and apoptotic effects of sulfonamide derivative compounds on human colorectal cancer cell lines

Colon and rectal cancers are the third most common type of cancer worldwide, and colon cancer is more common than rectal cancer. HDAC activators are best characterized as anticancer agents and are known to be important tools in a wide variety of physiological and pathological systems. Especially in cancer treatment methods, the discovery of compounds that have low side effects in healthy cells, and high cytotoxic activity in cancer cells is important. In this study; The aim of this study was to investigate the biological activities of sulfonamide-derived compounds with histone deacetylase activity in HT-29 (human colorectal adenocarcinoma), DLD-1 (human colon adenocarcinoma) and CCD-18Co (normal colon epithelium) cell lines. In these cell lines, the cytotoxic dose and IC50 value of the compounds were determined by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method. Bcl-2, Bax, Caspase-3, Caspase-8 and Caspase-9 mRNA levels, which are proteins that play an important role in apoptotic cell death and related signaling pathways, were analyzed by qRT-PCR method, P38/MAPK and ERK1 protein analyzes by Western blot method, HDAC activity feature HDAC activity was measured using an analysis kit. It was determined that these compounds have cytotoxic effects in HT-29 and DLD-1 cells, and their IC50 values were calculated between 1-31 μM. A significant increase in the Bax gene of apoptotic cell death; It was determined that Bcl-2, Caspase-3, Caspase-8 and Caspase-9 genes showed a significant decrease in their expressions. It was determined that the compounds showed a significant increase in p38/MAPK protein expression, which is involved in apoptosis-related pathways. The compounds were found to show HDAC activity in the HT-29 cell line. It is thought that sulfonamide derivative compounds may have anticancer activities and apoptosis-inducing effects in potential drug development studies.