Cannabinoids have been linked to anti-cancer activity through preliminary research. [1] However, the mechanisms through which they exert these effects remain hazy.
Cannabinoid-based therapies have been implicated in the management of different cancers, including pancreatic cancer. Pancreatic cancer is an aggressive form of cancer and accounts for 7% of cancer deaths in the US. It has a poor prognosis with a five-year survival of a mere 9%. Effective regimens for treating this form of cancer are also limited.
Immunotherapy is often used in the management of cancer. This process involves modulating the immune system through mechanisms such as immune checkpoint blockade with the aim of improving patient outcomes. However, efficacy appears limited for pancreatic cancer as the tumors are immunosuppressive, or resistant to the immune system. [2]
A recent study [2] conducted by researchers from Australia and China has helped shed light on how tetrahydrocannabinol (THC) and cannabidiol (CBD) may influence pancreatic cancer.
The study used cell lines and mouse models of pancreatic cancer. The cannabinoids inhibited the pancreatic cancer cells from growing and hence slowed down the cancer’s progression.
The following was demonstrated:
- THC and CBD inhibited the proliferation of human pancreatic cancer cells. CBD showed a stronger inhibitory effect compared to THC. THC had a stronger inhibitory action on cancer cells than pancreatic stellate cells; no difference was observed in CBD.
- P-21 activated kinase 1 (PAK1) knockout blocked the inhibitory effects of CBD and THC on pancreatic cancer cells, confirming this pathway as the mechanism of action.
- PAK1 knockout also blocked the inhibitory effects of cannabinoid oil (1:1 ratio of CBD:THC, by Aurora) on the growth of pancreatic tumors as demonstrated using a mouse model. This further shows the involvement of the PAK1 pathway in cannabinoid activity against pancreatic cancer.
- THC and CBD down-regulate PAK1 and thus limit the expression of pancreatic cancer cells.
From this research, it emerged clearly that the cannabinoids inhibited the cancer via the PAK1 mediated pathway. PAK-1 promotes the progression, growth, and proliferation of pancreatic cancer through signaling; it is also associated with the ability of tumors to suppress immune response.
THC and CBD also limited the expression of programmed death ligand 1 (PD-L1) proteins. PD-L1 proteins stop immune cells from killing cancer cells. Thus, the cannabinoids enhance the immune checkpoint blockade. [2]
As much as this investigation was preliminary, it can serve as a basis for future research in this area. It is ideal that randomized clinical trials be conducted to paint a true picture on how these cannabinoids can be used to help manage pancreatic cancer.
Image Source
OpenStax College – Anatomy & Physiology, Wikimedia Commons, Connexions Web site, CC BY 3.0
References
- Dariš B, Verboten MT, Knez Ž, Ferk P. Cannabinoids in cancer treatment: Therapeutic potential and legislation. Bosnian Journal of Basic Medical Sciences. 2019;19(1):14–23. Journal Impact Factor: 2.05, Times Cited: 27 (Semantic Scholar)
- Yang Y, Huynh N, Dumesny C, Wang K, He H, Nikfarjam M. Cannabinoids inhibited pancreatic cancer via P-21 activated kinase 1 mediated pathway. International Journal of Molecular Sciences. 2020;21(21):8035. Journal Impact Factor: 4.556, Times Cited: n/a
