Recent Patents on Anti-Cancer Drug Discovery

Author(s): Caroline Morin, Samuel Fortin, Andre M. Cantin, Marco Sirois, Chantal Sirois, Edmond Rizcallah and Eric Rousseau

DOI: 10.2174/1574891X113089990032

Anti-Cancer Effects of a New Docosahexaenoic Acid Monoacylglyceride in Lung Adenocarcinoma

Page: [319 - 334] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advances in research, diagnosis and treatment, lung cancer remains a highly lethal disease, often diagnosed at advanced stages and with a very poor prognosis. Therefore, new strategies for the prevention and treatment of lung cancer are urgently needed. The aim of the present study was to determine the anti-tumorigenic effects of docosahexaenoic acid monoacylglyceride (MAG-DHA), a newly patented DHA derivative in lung adenocarcinoma. Our results demonstrate that MAG-DHA treatments decreased cell proliferation and induced apoptosis in A549 human lung carcinoma cells whereas MAG-DHA treatment did not induce apoptosis of normal bronchial epithelial BEAS-2B cells. MAG-DHA decreased NFκB activation leading to a reduction in COX-2 expression level in both A549 cells and lung adenocarcinoma tissues. Furthermore, MAG-DHA treatment increased PTEN expression and activation concomitant with a decrease in AKT phosphorylation levels and enhanced apoptosis. Oral administration of MAG-DHA significantly reduced tumor growth in a mouse A549 xenograft model. Lastly, MAG-DHA markedly decreased COX-2 and enhanced PTEN protein expression in tumor tissue sections. Altogether, these data provide new evidence regarding the mode of action of MAG-DHA and strongly suggest that this compound could be of clinical interest in cancer treatment.

Keywords: Apoptosis, COX-2, DHA, lung adenocarcinoma, PTEN.