Cannabidiol (CBD) as a Promising Anti-Cancer Drug Through Activation of Endoplasmic Reticulum (ER) Stress Mechanisms

Student Presenter(s): Ariel Shaddaie and Samantha Cornwell
Faculty Mentor: Dong Zhang
School/College: Osteopathic Medicine, Old Westbury

Cannabidiol (CBD)’s potential as a promising anti-cancer drug is attributed to its low toxicity levels and its ability to inhibit the growth of certain cancers in mouse tumor models. The endocannabinoid receptors, CB1 and CB2, play a crucial role in regulating cellular calcium homeostasis in the cytoplasmic and endoplasmic reticulum (ER) membranes, and CBD affects these receptors. The Unfolded Protein Response (UPR) pathway is activated if there is prolonged ER stress, and it targets cells for apoptosis, this pathway is the target of CBD. In our study, we used Western blotting to investigate the effects of CBD on melanoma and normal skin fibroblast cells. Our multi-cancer project validated RNA-sequence data on multiple cancer cells treated with 5 μM CBD, showing upregulation of CHOP and PARP in A375 cells. These markers, both CHOP and PARP, are indicative of activation of the UPR pathway, which is associated with CBD-induced apoptosis. Different cancer cell lines have varying sensitivity to CBD-induced apoptosis, with A375 melanoma cells requiring a concentration of CBD (1.087 μM) to induce apoptosis. We are continuing to investigate the effects of CBD on other cell lines and are developing a staining technique to evaluate its impact on normal skin fibroblast cells.