“Cannabinoids are potential anticancer agents for the add-on treatment of malignant tumors.
Here, the effects of the previously less-explored non-psychoactive phytocannabinoids cannabigerol (CBG) and cannabichromene (CBC) on survival, apoptosis, and mitochondrial function were assessed in A549 and H460 lung cancer cells.
CBG and CBC triggered concentration-dependent cell death, autophagy, and mitochondrial apoptosis in both cell lines, with apoptosis indicated by Annexin V staining, activation of caspase-8, -9, and -3/7, loss of mitochondrial membrane potential, and elevated cytosolic levels of mitochondrial cytochrome c. CBG also upregulated ATF4, a stress-responsive transcription factor involved in autophagy and apoptotic signaling, and enhanced PARP cleavage. Both cannabinoids increased mitochondrial superoxide formation and reduced the mitochondrial oxygen consumption rate, with CBG additionally decreasing NDUFB8, a subunit of respiratory chain complex I.
Pharmacological receptor modulation showed that CBG- and CBC-induced cell death occurred independently of CB1, CB2, TRPV1, TRPM8, and PPARγ, whereas CBG-mediated cell death relied on PPARα, which also contributed to its apoptotic effects.
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.”
https://pubmed.ncbi.nlm.nih.gov/42352060
“There is now substantial preclinical evidence supporting an anticancer action of various cannabinoids in different tumor entities.”
“This study investigates the effects of CBG and CBC on lung cancer cell survival, apoptosis, and mitochondrial function and bioenergetics, with particular emphasis on the role of PPARα in this process.
Here, we show convincing cytotoxic, pro-apoptotic and mitochondrial toxic effects of both cannabinoids.
More importantly, this study demonstrates for the first time a mediating role of PPARα in the induction of tumor cell death and apoptosis by CBG, which makes this non-psychoactive phytocannabinoid an interesting compound in the search for new targeted therapies for the treatment of malignant tumors.”
“The non-psychoactive phytocannabinoids CBG and CBC, which remain comparatively underexplored, were shown to induce pronounced pro-apoptotic effects and mitochondrial dysfunction in the human lung cancer cell lines A549 and H460, with CBG acting via the transcription factor PPARα to promote apoptotic cell death.”