Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling

An estimated 60% of melanoma patients develop melanoma brain metastases (MBMs). However, the molecular factors that govern the growth of MBMs are still unknown. The excitatory neurotransmitter glutamate has been shown to control the proliferation of various types of cancer cells within the brain parenchyma, but the cellular sources and molecular mechanisms involved in this process remain unclear. By their well-known role in inhibiting synaptic glutamate release, cannabinoid CB1 receptors (CB1Rs) located on glutamatergic nerve terminals are conceivably well-positioned to control the growth of MBMs. In silico data mining in cancer-genome atlases and in vitro studies with melanoma cell lines supported that a glutamate-NMDA receptor axis drives melanoma cell proliferation. Strikingly, grafting melanoma cells into the brain of mice lacking CB1Rs selectively in glutamatergic neurons increased tumour size and concomitantly activated NMDA receptors on tumour cells. Altogether, our findings reveal an unprecedented role of neuronal CB1Rs in controlling MBMs.

Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment

Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa’s biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.

Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment

Schanknecht, E., Bachari, A., Nassar, N., Piva, T., & Mantri, N. (2023). Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment. International Journal of Molecular Sciences, 24(1), 859.

Impact of Cannabinoid Compounds on Skin Cancer

Recent research has suggested that the endocannabinoid system offers several pharmacotherapeutic targets for drug administration as new options for the treatment and prophy- laxis of skin cancer. This review focused on the anticarcinogenic mechanisms of cannabinoids at the different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy.

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

Authors: Golnaz Vaseghi, Mohamad Javad Taki, Shaghayegh Haghjooy Javanmard
Iranian journal of basic medical sciences, October 2017

OBJECTIVES: Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized…