Researchers from the Universidade do Porto have identified promising anti-cancer properties in four lesser-known cannabinoids: cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC).
The study, published in Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids, finds that these cannabinoids may play a potential role in treating estrogen receptor-positive (ER+) breast cancer.
The research focused on the effects of CBG, CBDV, CBN, and CBC using both 2D and 3D models of ER+ breast cancer, specifically the MCF-7aro cell line. These minor cannabinoids were found to interfere with cancer cell proliferation, disrupt cell cycle progression, and induce apoptosis through distinct pathways. Among the compounds tested, CBN produced the most significant anti-tumor response.
According to the authors, “CBG exerts its effects through a down-regulation of both ER and AR protein levels, while CBDV reduces aromatase protein levels. CBN and CBC simultaneously affect the three targets, ER, aromatase, and AR.” The study adds that these cannabinoids impaired cancer cell growth by acting as ER negative regulators, downregulating aromatase levels, and initiating AR-dependent cell death.
The authors conclude: “Although all the cannabinoids affected the growth of MCF-7aro spheroids, CBN caused the most pronounced effect… this is the first in vitro study that unveils the effects, mechanism of action, and targets of these minor cannabinoids in luminal A breast cancer cases.”
The findings expand the scientific understanding of minor cannabinoids, showing that their impact extends beyond traditional compounds like THC and CBD. The researchers suggest these phytocannabinoids may have therapeutic relevance not only for ER+ breast cancer but potentially for other diseases that depend on similar hormonal pathways.
The study concludes:
Here, we demonstrated that four minor phytocannabinoids, namely CBG, CBDV, CBN, and CBC exert relevant anti-cancer effects in 2D and 3D ER+ breast cancer models. The mechanism of action by which CBG may exert its anti-proliferative and cell death effects involves the downregulation of both ER and AR protein levels, while CBDV only reduces aromatase protein levels. Regarding CBN and CBC, their anti-cancer effects are the result of a simultaneous effect on the three targets, ER, aromatase, and AR. In fact, to impair breast cancer growth, these cannabinoids present an AR-dependent cell death, down-regulate aromatase protein levels, and act as ER negative regulators. Notably, although all the cannabinoids affected the growth of MCF-7aro spheroids, CBN caused the most pronounced effect.
Overall, by exploring the mechanisms of action of some less known phytocannabinoids in specific targets, this study expands the knowledge regarding the anti-cancer potential of cannabinoids and boosts the idea that these compounds might be applied not only in ER+ breast cancer treatment, but also in other diseases relying on the same signaling pathways. It should be highlighted that to best of our knowledge, this is the first in vitro study that unveils the effects, mechanism of action, and targets of these minor cannabinoids in luminal A breast cancer cases.
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