The Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and its Modulation by Lysophosphatidylino-sitol in Human Breast Cancer Cells

Abstract

2-arachnadoyl glycerol (2-AG) is one of the most common endocannabinoid molecules with antiproliferative, cytotoxic and pro-proliferative effects on different types of tumors. Typically, it induces cell death via CB1/CB2-linked ceramide production. In breast cancer, ceramide is counterbalanced by the sphingosine-1-phosphate, and thus the mechanisms of 2-AG influence on proliferation are poorly understood. In this paper, we evaluated the mechanism of the cell death induction by 2-AG and the influence of LPI on it in 6 human breast cancer cell lines of different tumor degree using a novel analog, 2-arachidonoyl-difluoropropanol (2-ADFP). 2-ADFP induced cell death via the CB2 and TRPV1-dependent COX-2 induction and oxidized metabolites production. The activity was enhanced by LPI.