“Cholangiocarcinomas are devastating cancers of biliary origin with limited treatment options…
Marijuana and its derivatives have been used in medicine for many centuries, and presently there is an emerging renaissance in the study of the therapeutic effects of cannabinoids…
In addition, cannabinoids might be effective antitumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture and in laboratory animals.
Modulation of the endocannabinoid system is being targeted to develop possible therapeutic strategies for a number of cancers; therefore, we evaluated the effects of the two major endocannabinoids, anandamide and 2-arachidonylglycerol, on numerous cholangiocarcinoma cell lines…
These findings suggest that modulation of the endocannabinoid system may be a target for the development of possible therapeutic strategies for the treatment of this devastating cancer.
Consistent with our observation that AEA has antiproliferative and proapoptotic properties, cannabinoids of various origins (endogenous, plant-derived, or synthetic analogues) have been shown to suppress cancer cell growth in vitro as well as in vivo.
In conclusion, we have clearly demonstrated opposing actions of the endocannabinoids AEA and 2-AG on cholangiocarcinoma cell proliferation and have shown that these actions are via a cannabinoid receptor-independent but lipid raft-mediated pathway. Furthermore we have shown that the antiproliferative/proapoptotic actions of AEA are mediated via an accumulation of ceramide and the recruitment of the Fas death receptor into the lipid rafts. Cholangiocarcinoma has a very poor prognosis and survival rate; therefore we propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA would prove beneficial for the treatment of this devastating disease.”