Molecular Evidence Linking Cannabidiolic Acid to Breast Cancer Growth Inhibition
Cannabinoids have been suggested to play a key role in certain cancers. These data are based in part on the presence of high levels of cannabinoid 2 receptors (CB2) on immune cells compared to other cell types in the body. Additional data has suggested that CB2 is also highly expressed in cancer cells and thus may play a role in its pathogenesis. (1)
CB2 is linked to synthesis of ceramide, which is associated with the proto-oncogene serine/threonine-protein kinase, or RAF1. Downstream of RAF-1 is p42/p44 MAPK; sustained over time, activation of p42/p44 MAPK leads to apoptosis in glioma cells. This process can be blocked using CB agonists. (1)
Since multiple cannabinoids bind to CB2s, studies have investigated their ability to inhibit growth of cancer cells. And such studies have indicated that cannabidiolic acid (CBDA), a precursor to CBD, may be effective against breast cancer specifically.
CBDA was found to inhibit COX-2, which is highly expressed in invasive breast cancers, and may suppress genes related to cancer growth. (2) In addition, another study reported an association between CB2 expression in HER2+ breast tumors and poor prognosis. (3) These data suggest that CBDA via CB2 could potentially prevent breast cancer growth.
Another study found that CBDA inhibited migration of invasive MDA-MB-231 human breast cancer cells via a CB-independent pathway. These effects were associated with suppressing cAMP-dependent protein kinase A and activating RhoA, a small GTPase. (4)
While additional studies are needed to substantiate these effects, taken together, they contribute to the growing literature supporting cannabinoids as potential anti-cancer therapies.
- Kisková, T., et al. “Future Aspects for Cannabinoids in Breast Cancer Therapy.” Int J Mol Sci, vol.20, no.7, 2019, pp. 1-21.
- Takeda, S., et al., “Down-regulation of Cyclooxygenase-2 (COX-2) by Cannabidiolic Acid in Human Breast Cancer Cells.” J Toxicol Sci, vol.39, no. 5, 2014, pp. 711-716.
- Pérez-Gómez, E., et al., “Role of Cannabinoid Receptor CB2 in HER2 Pro-oncogenic Signaling in Breast Cancer.” JNCI, vol.107, no.6, 2015, pp. 1-13.
- Takeda, S., et al., “Cannabidiolic Acid, A Major Cannabinoid in Fiber-type Cannabis,
- Is an Inhibitor of MDA-MB-231 Breast Cancer Cell Migration.” Toxicol Lett, vol.214, no.3, 2012, pp. 314-319.