Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

“Breast cancer is the leading cause of cancer-related deaths among women aged 34–50 worldwide, and is the most commonly diagnosed metastasizing tumor in women of all ages. Despite advances in understanding breast cancer as a disease, there remains a critical need for novel disease-modifying therapeutics.

Nonspecific cannabinoids, cannabinoid receptor 2 (CB₂)-selective, as well as cannabinoid receptor 1 (CB₁)-selective compounds have yielded similar antitumor results in several tumor models. The lack of neuronal expression of CB₂ receptors precludes CB₂ selective compounds from inducing the psychotropic effects that typically accompany CB₁ activation.

 Our group and others have shown that CB₂ agonists displaying selectivity for the CB₂ receptor can decrease tumor cell viability and significantly attenuate cancer-induced bone pain without displaying psychoactive or addictive properties.

…antitumor effects of cannabinoids have been demonstrated in a variety of tumor models…

The antiproliferative effects of a CB₂ agonist along with our previous work demonstrating significant efficacy in inhibiting bone cancer pain and slowing bone loss in a murine model of advanced breast cancer strongly suggest that CB₂ agonists should be investigated in humans as adjunct therapy for advanced stages of breast cancer.

 Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB₁) or cannabinoid receptor 2 (CB₂), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems.

The results of this work characterize the actions of a CB₂-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.

Several groups have shown that both nonselective cannabinoid and CB₂-specific compounds decrease breast cancer viability in vitro and in vivo: Δ⁹-tetrahydrocannabinol and CB₂-selective agonist, JWH-133, have been demonstrated to exert considerable antitumoral effects…”