The current state and future perspectives of cannabinoids in cancer biology

Abstract

To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids' anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells' proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.

Keywords: CBD; THC; Cancer; Cannabidiol; Cannabinoids; Cannabis; Tetrahydrocannabinol.

Figure 1

The known mechanisms responsible for the induction of apoptosis by cannabinoids. CBD, cannabidiol; THC, Δ⁹‐tetrahydrocannabinol; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; TRPV1, receptor potential channel subfamily V member 1; GPR55, orphan G‐protein coupled receptor 55; ROS, reactive oxygen species; ER, endoplasmic reticulum; p8, protein p8 (Nuclear Protein 1, NUPR1); CHOP, CCAAT/‐enhancer‐binding protein homologous protein; ATF4, activating transcription factor 4; TRIB3, tribbles pseudokinase 3; Akt, protein kinase B; mTORC1, mammalian target of rapamycin C1; p21, cyclin‐dependent kinase inhibitor 1; p27, cyclin‐dependent kinase inhibitor 1B; CDK, cyclin‐dependent kinase; pRb, retinoblastoma protein.