“Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process.
As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells.
In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner.
Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction.
Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD.”
https://pubmed.ncbi.nlm.nih.gov/39910152/
“Preclinical studies have demonstrated that CBD, either as a monotherapy or in conjunction with other treatments, holds potential as a novel anti-tumor, anti-inflammatory, and analgesic agent. Our results demonstrated that CBD promoted OC cells apoptosis and G0-G1 phase arrest by disrupting the CBR1-mediated lipid metabolism and ER stress- and mitochondrial dysfunction-associated apoptosis signaling pathways (Fig. 8). Therefore, CBD may serve as a potential candidate for adjuvant therapy in the treatment of ovarian cancer. However, larger-scale clinical studies involving more patient samples and detailed dose-response relationship analyses are still needed to confirm the efficacy of CBD in cancer patients.”