“Currently, use of cannabinoids is limited to improve adverse effects of chemotherapy and their palliative administration during treatment is curiously concomitant with improved prognosis and regressed progression in patients with different tumor types. Although, non-psychoactive cannabidiol (CBD) and cannabigerol (CBG) display antineoplastic effects by repressing tumor growth and angiogenesis both in cell line and animal models, their use as chemotherapeutic agents is awaiting further investigation. Both clinical and epidemiological evidence supported by experimental findings suggest that micronutrients such as curcumin and piperine may present a safer strategy in preventing tumorigenesis and its recurrence. Recent studies demonstrated that piperine potentiates curcumin’s inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity. In this study, we investigated a plausible therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine in the colon adenocarcinoma using HCT116 and HT29 cell lines. Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line.”
https://pubmed.ncbi.nlm.nih.gov/37180710/
“This study demonstrates that combination of curcumin, piperine and cannabinoid variants inhibit cell proliferation and induce apoptosis drastically in distinct models of colorectal cancer. Intriguingly, our findings point out that the compounds of interest, each of which are already known for their anti-tumorigenic and preventive role in colon cancer as single agents, displayed an augmented therapeutic effect in the cell lines tested. In the HT29 cell line, CBG significantly reduced cell proliferation and induced apoptosis as a monotherapy agent, whereas these anti-tumorigenic effects were overridden in the presence of curcumin/piperine. Therefore, findings from this study suggest a benefit in using cannabinoid compounds as single anti-cancer agents in the treatment of those colon carcinoma tumors that carry a genetic profile similar to that of the HT29 cell line. One major limitation of the current study was to reconcile these findings with the cannabinoid receptor 1 (CB1 receptor) and cannabinoid receptor 2 (CB2 receptor) expression profile of the cell lines used. Therefore, in future studies the link between the anti-tumorigenic effects of single cannabinoid compounds or their cocktails and the cannabinoid receptor expression should be interrogated to shed light on the differences in the responses of these cells to distinct cannabinoid-based regimens. In addition to the cannabinoid receptor status, role of other mutations in driver genes should be subject to more rigorous mechanistic studies to fully understand their role in determining the drug mechanism of action and the response to distinct treatment schemes involving cannabinoids as single agents their various combinations.”
https://www.frontiersin.org/articles/10.3389/fphar.2023.1145666/full