Whynot, E. G. | Search bioRxiv

bioRxiv2021

Anti-cancer potential of cannabis terpenes in a taxol-resistant model of breast cancer

Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aims to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and if their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and {beta}-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and {beta}-myrcene. Combinations of nerolidol and {Delta}9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.

cancer biology↗

bioRxiv2021

Anti-cancer properties of cannabidiol and Δ9-tetrahydrocannabinol and potential synergistic effects with gemcitabine, cisplatin and other cannabinoids in bladder cancer

IntroductionWith the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and {Delta}9-tetrahydrocannabinol with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce desirable synergistic effects. We also evaluated whether co-treatment of different cannabinoids also generated synergistic effects. Materials and MethodsWe generated concentration curves with different drugs to identify the range at which they could exert anti-tumor effects. We also evaluated the activation of the apoptotic cascade and whether cannabinoids have the ability to reduce invasion. ResultsCannabidiol, {Delta}9-tetrahydrocannabinol and other cannabinoids reduce cell viability of bladder cancer cell lines, and their combination with gemcitabine or cisplatin may induce differential responses: from antagonistic to additive and synergistic effects, depending on the concentrations used. Cannabidiol and {Delta}9-tetrahydrocannabinol were also shown to induce caspase 3 cleavage and reduce invasion in a Matrigel assay. Cannabidiol and {Delta}9-tetrahydrocannabinol also display synergistic properties with other cannabinoids like cannabichromene or cannabivarin. DiscussionOur results indicate that cannabinoids can reduce human bladder transitional cell carcinoma cell viability, and that they can potentially exert synergistic effects when combined with other agents. Our in vitro results will form the basis for future studies in vivo and in clinical trials for the development of new therapies that could be beneficial for the treatment of bladder cancer in the future.

cancer biology↗