It is widely accepted that endocannabinoids, as part of the endocannabinoid system (ECS), play a vital role in maintaining human health. For hundreds of years, the cannabis plant has provided medicinal value, despite its poorly understood mechanisms. Recent decades of research and scientific evaluation have proven to elucidate some of these mechanisms, including some of the components included in the ECS.
Endocannabinoids and their receptors, CR1 & CR2, have been described in the literature but experts believe that large gaps still exist in our current understanding related to the cellular and molecular interactions between cannabinoids, their receptors, broad physiological systems, and individual effects based on organism species.
Current knowledge of the ECS includes its involvement in lessening inflammation, immune system modulation, analgesia, anti-tumor actions, and more. Researchers collaborated to publish a new connection between the CB2 cannabinoid receptor and its ability to inhibit cell growth in renal cell carcinoma (RCC) in vitro. Their work was published May 23, 2018 in BMC Cancer. The purpose of the study was to explore the ECS and its role in RCC by evaluating CB1 & CB2 expression. The research demonstrated that RCC cells express both CB1 & CB2. They observed anti-proliferative action attributed to CB1 and CB2 but had to determine which receptor was contributing to inhibition of cancerous proliferation. Using cannabinoid receptor agonists, the group pharmacologically blocked the receptors one at a time. Findings revealed that CB2 reduced proliferation of the RCC cells but did not alter or affect non-cancerous cells. The synthetic cannabinoid that binds to both CB1 and CB2, WIN-55, inhibited proliferation of RCC primary and metastatic cells. The apparent selectivity of controlled synthetic cannabinoid application targets cancer cells in a way that is not well understood. Multiple different RCC cancer lines were inhibited by the synthetic cannabinoid and, in fact, increased apoptosis was observed by flow cytometric analysis.
One of the greatest challenges of RCC is that these tumor cells can quickly metastasize, and treatment become especially challenging. One of the protective biological features of RCC is its ability to form cancer spheres. The RCC cells physically morph into spherical shape and take on stem-cell characteristics. The synthetic cannabinoid, WIN-55, was found to prevent the formation of these changes which leads researchers to wonder about cannabinoid use for hindering RCC metastasis in the body.
Lastly, this study investigated the role of WIN-55 in arresting RCC cells in G0/G1 so they could not proliferate. It is believed that WIN-55 plays a role in activation of the PI3K/AKT/mTOR signaling pathway, which is involved in cell proliferation and cellular survival in multiple different cancer types.
This research is promising for cancer therapies; cannabinoids, synthetic or naturally derived from medical cannabis plants, continue to show their value in health and disease.