Cannabinoids fight pancreatic cancer

Cannabinoids which work via the CB1 and CB2 receptor, as does THC from marijuana, interfere with pancreatic cancer's cellular metabolism, causing the cancer cells to die off. The following abstract is quite technical but what you need to consider is the final line which reports that cannabinoids killed off and stunted the growth of pancreatic cancer cells. Cell Death Dis. 2013 Jun 13;4:e664. doi: 10.1038/cddis.2013.151.Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells.Dando I, Donadelli M, Costanzo C, Dalla Pozza E, D'Alessandro A, Zolla L, Palmieri M.SourceDepartment of Life and Reproduction Sciences, Biochemistry Section, University of Verona, Verona, Italy. Abstract: The anti-tumoral effects of cannabinoids have been described in different tumor systems, including pancreatic adenocarcinoma, but their mechanism of action remains unclear. We used cannabinoids specific for the CB1 ACPA and CB2 GW receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMPK activation induced by a ROS-dependent increase of AMP/ATP ratio. ROS promote nuclear translocation of GAPDH, which is further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determine the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibits the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway leads to decreased activity of both the pyruvate kinase isoform M2 PKM2, further downregulating glycolysis, and glutamine uptake. Altogether, these alterations of pancreatic cancer cell metabolism mediated by cannabinoids result in a strong induction of autophagy and in the inhibition of cell growth.

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