Cannabidiol Affects Extracellular Vesicle Release, miR21 and miR126, and Reduces Prohibitin Protein in Glioblastoma Multiforme Cells.

 Translational Oncology“Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant brain tumor in adults, with poor prognosis. Extracellular vesicles (EVs) are key-mediators for cellular communication through transfer of proteins and genetic material. Cancers, such as GBM, use EV release for drug-efflux, pro-oncogenic signaling, invasion and immunosuppression; thus the modulation of EV release and cargo is of considerable clinical relevance. As EV-inhibitors have been shown to increase sensitivity of cancer cells to chemotherapy, and we recently showed that cannabidiol (CBD) is such an EV-modulator, we investigated whether CBD affects EV profile in GBM cells in the presence and absence of temozolomide (TMZ). Compared to controls, CBD-treated cells released EVs containing lower levels of pro-oncogenic miR21 and increased levels of anti-oncogenic miR126; these effects were greater than with TMZ alone. In addition, prohibitin (PHB), a multifunctional protein with mitochondrial protective properties and chemoresistant functions, was reduced in GBM cells following 1 h CBD treatment. This data suggests that CBD may, via modulation of EVs and PHB, act as an adjunct to enhance treatment efficacy in GBM, supporting evidence for efficacy of cannabinoids in GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/30597288

Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa and known for its anti-neoplastic and chemo-preventive activities. Known anti-cancerous effects of cannabinoids include inhibition of tumor proliferation, angiogenesis and induction of tumor cell death, while in GBM, additional effects on inhibition of invasiveness and stem-cell like properties have been observed. CBD has also been shown to selectively inhibit GBM proliferation and to induce death of cultured human GBM cells, as well as being effective against other cancers.  We have recently shown that CBD is a novel modulator of EV release in several cancer cell lines and we and other groups have shown that EV-modulators, including CBD, can significantly increase sensitivity of various cancer cells to chemotherapy. This supports emerging evidence that CBD has anti-cancer effects and indicates that CBD can be used to lower anti-chemotherapeutic responses to TMZ as well as modifying EV cargo to an anti-oncogenic signature in GBM.”

https://www.sciencedirect.com/science/article/pii/S1936523318305990?via%3Dihub

Cannabis for cancer – illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology.

Publication Cover “A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes. Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines. Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids were classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia and anxiety are presented. Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related. Expert opinion: Sufficient evidence supports use of Cannabis for palliative indications in oncology, however, patients should be carefully selected, guided and followed. Promising research suggests potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.” https://www.ncbi.nlm.nih.gov/pubmed/30572744 https://www.tandfonline.com/doi/abs/10.1080/13543784.2019.1561859?journalCode=ieid20
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