Cytotoxic and apoptotic effects of ceranib-2 offering potential for a new antineoplastic agent in the treatment of cancer cells

Abstract

Fibrocarcinomas are malignant tumours that originate in mesenchymal cells. The tumours typically form in the presence of connective tissue and are of key consideration when assessing research priorities for future healthcare management. Ceramidase inhibitors, such as ceranib-2, have demonstrated capacity to interfere with cellular DNA functionality, initiating apoptosis in many cancer cell lines. The enzyme ceramidase can regulate cellular levels of sphingosine and sphingosine-1-phosphate by controlling hydrolysis of ceramide. The present study investigates the antigrowth effects of ceranib-2 on mouse embryonic fibroblast cells (NIH/3T3 normal cell line) and rat embryonic fibroblast cells (5RP7 cancer cell line). Research was conducted using colorimetric 3-(4,5-dimethylthiazol-2-yl)2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, confocal microscopy, and transmission electron microscopy. The results indicate that in vitro fibrocarcinomas have the potential to undergo apoptotic death when influenced by the antigrowth behaviour of ceranib-2. This is true even of cells exposed only to minimal doses of ceranib-2. Indicators of apoptotic death, specifically presentation of a pyknotic nucleus, were observed by confocal micrographs in treated cells double-stained with acridine orange and Alexa Fluor-488 Phalloidin. It is theorised that ceranib-2 will function in accordance with the antiproliferative activity of other acid ceramidases, ultimately resulting in the molecule's classification as a new antitumour agent.