Cannabinoids in the landscape of cancer

Abstract

Introduction Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties. Method A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types. Results Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2. Conclusion Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.

Role of Caryophyllane Sesquiterpenes in the Entourage Effect of Felina 32 Hemp Inflorescence Phytocomplex in Triple Negative MDA-MB-468 Breast Cancer Cells

“…Regarding cannabidiol, it is known to act as a multitarget agent, being an inverse agonist of CB2 receptor, and an antagonist of the non-cannabinoid GPR55 receptor, the transient receptor potential cation channel subfamily M member 8 (TRPM8), and the T-type Ca 2+ channels; moreover, it has been shown to inhibit the fatty acid amide hydrolase (FAAH), responsible for the degradation of anandamide, and the fatty acid-binding protein (FABP), which favors the uptake of anandamide into cell, making it available for intracellular targets, such FAAH or nuclear PPARγ [35,42]. These mechanisms lead to an increased extracellular anandamide concentration, which can indirectly activate CB1 and CB2 receptors [35,42].…”

Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells

“…The length of the alkyl side chain may affect the affinity for some biological targets as it has been demonstrated for THC, which is a CBD isomer [ 22 ]. Furthermore, due to their implication in the control of cell growth and death, cannabinoids have been proposed as a new adjuvant in cancer therapy of various malignancies, such as prostate and breast cancer [ 17 , 28 ]. As already described, phytocannabinoids may act via dependent and/or independent cannabinoid receptor mechanisms [ 13 , 15 ].…”

“…This increase led to the reduction of the mitochondrial transmembrane potential, the opening of the mitochondrial permeability transition pore (mPTP) with subsequent release of cytochrome C into the cytoplasm [ 33 , 34 ], finally resulting in the activation of the mitochondrial-dependent apoptosis pathway. The apoptotic event is preceded by the cell cycle arrest in various cancer models [ 1 , 17 , 35 ]. Another recent study confirmed that the CBD treatment triggered multiple intracellular effects in MCF-7 cells, such as increased Ca 2+ levels, ROS accumulation and ER stress, finally leading to the induction of apoptosis [ 14 ].…”

“…In line with the literature [18,23,24], this is a working concentration that induces biological responses without dramatic effects on cell viability. An increase in the oxidative stress has been detected in cancer cells after CBD treatment due to a massive increase of ROS production that leads to the activation of apoptosis and autophagy [14,16,17]. Starting from these data, we analyzed ROS levels in MCF-7 cells treated with 10 µM nat CBD, syn CBD, CBDB and CBDP for 24 h using the 2 ,7dichlorodihydrofluorescein diacetate (DCFH-DA) staining.…”

“…These are G-protein coupled receptors (GPCR) that can be activated by endogenous and exogenous cannabinoids. More recently, studies have shown that cannabinoids can activate other receptors, i.e., GPR55, TRPM8 as well as other ion channels of the transient receptor potential superfamily as vanilloid type 1–4 (TRPV1, TRPV2, TRPV3 and TRPV4) [ 12 , 14 , 15 , 16 , 17 ]. In the context of breast cancer, the biological role of CBD in the regulation of epithelial tumor pathophysiology has clearly emerged [ 18 , 19 ].…”