Receptor-dependent and receptor-independent endocannabinoid signaling: A therapeutic target for regulation of cancer growth

Abstract

The endocannabinoid system comprises the G-protein coupled CB1 cannabinoid receptor (CB1R) and CB2 cannabinoid receptor (CB2R), their endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and catabolism. Recent works have revealed several important interactions between the endocannabinoid system and cancer. Moreover, it is now well established that synthetic small molecule cannabinoid receptor agonist acting on either CB1R or CB2R or both exert anti-cancer effects on a variety of tumor cells. Recent results from many laboratories reported that the expression of CB1R and CB2R in prostate cancer, breast cancer, and many other cancer cells are higher than corresponding non-malignant tissues. The mechanisms by which cannabinoids acting on CB1R or CB2R exert their effects on cancer cells are quite diverse and complex. Further, several studies demonstrated that some of the anti-proliferative and apoptotic effects of cannabinoids are mediated by receptor-independent mechanisms. In this minreview we provide an overview of the major findings on the effects of endogenous and/or synthetic cannabinoids on breast and prostate cancer. We also provide insight into receptor independent mechanisms of the anti-cancer effects of cannabinoids under in vitro and in vivo conditions.

Engineering of Δ 9 -tetrahydrocannabinol delivery systems based on surface modified-PLGA nanoplatforms

“…Cell viability strongly depends on: (i) the 9 -THC concentration in contact with Caco-2 cells; (ii) the incubation time; and, (iii) the type of 9 -THC-based formulation (F = 26.647, p < 0.05, n = 140), which is in agreement with previously published investigations [4,23,51,52]. The factor of analysis of variance pointed out significant interactions of the 9 -THC concentration with the incubation time (p < 0.05) and with the type of 9 -THC-based formulation (p < 0.05).…”

Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration

“…A number of in vitro and murine models have shown that the CANNs CBD and THC can alter the way that tumour cells proliferate, as well as increase the capacity of these cells to undergo death by apoptosis and/or autophagy. These effects appear to be both dependent and independent of signalling via their cognate CBR (13,20). More recently, in the context of glioma, CANNs have also been shown to enhance the action of other treatment modalities such as chemotherapy and irradiation in vivo (7,8).…”

Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer

“…The endocannabinoid system is thought to be important in the regulation of cancer cell apoptosis, proliferation, migration, adhesion and invasion. Increased expression of the cannabinoid receptors (CB1R and CB2R) and FAAH has been documented in prostate and breast cancer and has been associated with worse outcomes [31]. FAAH inhibitors are under development for the treatment of pain and inflammation [31], but may also be useful in cancer.…”

“…Increased expression of the cannabinoid receptors (CB1R and CB2R) and FAAH has been documented in prostate and breast cancer and has been associated with worse outcomes [31]. FAAH inhibitors are under development for the treatment of pain and inflammation [31], but may also be useful in cancer. Our data suggests that FAAH inhibitors might be a potential targeted agent for obesity-driven cancers.…”