A new study published in Antioxidants found that the cannabinoids cannabigerol (CBG) and cannabichromene (CBC) induced cell death and apoptosis in two lung cancer cell lines, suggesting the compounds may warrant further research as potential add-on cancer therapies.

The study was conducted by researchers from Rostock University Medical Center and the University of Rostock. It examined how CBG and CBC affected A549 and H460 lung cancer cells, focusing on cell survival, apoptosis and mitochondrial function.

Researchers found that both cannabinoids triggered concentration-dependent cell death in the two lung cancer cell lines. The effects included signs of autophagy and mitochondrial apoptosis, with researchers observing activation of caspase-8, caspase-9 and caspase-3/7, loss of mitochondrial membrane potential and increased levels of mitochondrial cytochrome c in the cytosol.

CBG also increased ATF4, a stress-responsive transcription factor involved in autophagy and apoptotic signaling, while enhancing PARP cleavage, another marker associated with apoptosis. Both CBG and CBC increased mitochondrial superoxide formation and reduced mitochondrial oxygen consumption, suggesting an impact on mitochondrial function.

The study also found that CBG reduced NDUFB8, a subunit of mitochondrial respiratory chain complex I. Researchers said the findings point to mitochondrial dysfunction as one of the mechanisms involved in the cannabinoids’ effects on the cancer cells.

In examining how the cannabinoids produced these effects, researchers found that CBG- and CBC-induced cell death did not depend on CB1, CB2, TRPV1, TRPM8 or PPARγ. However, CBG’s effects were tied to PPARα, which researchers found also contributed to its apoptotic activity.

“In summary, CBG and CBC induce apoptosis and cell death in A549 and H460 cells, with PPARα mediating the effects of CBG, highlighting its potential as a therapeutic target,” the study states.