A new study reports that cannabinoids, when combined with melatonin and the chemotherapy drug cisplatin, may enhance anti-cancer effects against certain bone cancer cells while potentially allowing for lower cisplatin doses.
The study, published in Naunyn-Schmiedeberg’s Archives of Pharmacology, was conducted by researchers from Yozgat Bozok University and Erciyes University. It focused on osteosarcoma and chondrosarcoma, two forms of bone cancer that can be difficult to treat due in part to resistance to chemotherapy and the systemic toxicity associated with cisplatin.
Researchers examined the effects of cannabidiol (CBD), tetrahydrocannabinol (THC), melatonin and cisplatin on osteosarcoma cell lines MG63 and Saos2, as well as the chondrosarcoma cell line SW1353. Normal fibroblast and osteoblast cells were also used as controls.
According to the study’s abstract, several combination treatments produced synergistic effects, meaning the drugs worked better together than they would be expected to individually. The strongest results were seen with THC combined with cisplatin and melatonin, as well as cisplatin combined with melatonin. These combinations showed significant synergy in SW1353 and Saos2 cancer cells.
Researchers reported that the combinations allowed for a 2.77-fold to 4.38-fold reduction in the cisplatin dose while maintaining anti-cancer activity. This is notable because cisplatin, while widely used in cancer treatment, is associated with serious side effects that can limit its use.
The study also found that the synergistic treatments increased markers of apoptosis, a form of programmed cell death, in cancer cells. This included increased expression of Casp3, Casp8, Casp9 and Bax, along with signs of DNA fragmentation, chromatin condensation and mitochondrial disruption.
At the same time, normal cells showed minimal changes, suggesting a degree of selectivity toward cancer cells in the experimental setting.
Cannabinoids were also found to significantly reduce cancer cell migration and invasion, with the effects becoming stronger when used in combination treatments. Molecular docking analysis further suggested that the compounds may interact with multiple cancer-related targets, including COX-2, MMPs, ADAMTS-5 and proteins in the MAPK pathway.
The researchers concluded that melatonin may enhance cannabinoid-mediated sensitization to cisplatin through selective pro-apoptotic and anti-invasive mechanisms. They said the findings support further exploration of low-dose, multi-target combination strategies for bone sarcoma therapy.
However, the research was conducted in cell models, meaning additional animal studies and human clinical trials would be needed before any conclusions can be made about potential treatment use in patients.
