The effect of BZO-hexoxizid (MDA-19) on the PLA2G7, UCP2 and NEDD4L protein levels in the prostate cancer cell lines

As the second common type of cancer and laeding causes of death worldwide affcting males, Prostate Carcinoma (PCa) is considered as a hypoxic and lipogenic solid tumor. From cancer biochemistry aspects, metabolic programming, as well as dysregulated lipid metabolism are attributed to PCa, unlike many other cancers. It has been interrogated that PCa cells are potentiated to store lipids in the form of lipid droplets. According to the current ineffective therapeutic approches for PCa, there is an imperative need to the more effcacious approaches using basic medical sciences. As active compounds produced from Cannabis sativa L., Cannabinoids have been widely used in alternative medicine. There is a close connection between Cannabinoids and lipid metabolism, corroborating their anti-cancer properties, including induction of apoptosis, cell cycle arrest, and angiogenesis. Correspondingly, it has been demonstated that PLA2G7 is involved in lipid droplet formation by hydrolyzing phospholipids into fatty acids. In addition, UCP2 plays an indisputable role in the metablic switching through promoting fatty acid metabolism instead of glucose utilization. Moreover, NEDD4L is responsible for ligasing E3 ubiquitin, and protein degradation. Accordingly, in our study, the cytotoxic effects of MDA-19 on the expression levels of PLA2G7, UCP2 and NEDD4L proteins in two prostate cancer cell lines (DU145, PC3) were investigated. To evaluate the cytotoxic effects of MDA-19 on the expression levels of aforesaid proteins, the IC50 value was determined using the MTT test. Then, PCa cell lines were treated with various concentrations of MDA-19, for 24, 48 and 72 hours. Then, expression levels of aforementioned proteins were investigated through ELISA. A decreasing trend of the expression levels of PLA2G7 and UCP2, and an increasing trend of the expression levels of NEDD4L were repoted. In conclusion, it is stated that MDA-19 can be used as a potential therapeutic agent for the treatment of prostate cancer by affecting lipid droplet metabolism. Keywords: Cannabinoid, NEDD4L, PLA2G7, Prostate Cancer, UCP2