<i>In Vitro</i> Anticancer Activity of Plant-Derived Cannabidiol on Prostate Cancer Cell Lines

Abstract

Cannabinoids, the active components of Cannabis sativa Linnaeus, have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression, but their use in chemotherapy is limited by their psychotropic activity. To date, cannabinoids have been successfully used in the treatment of nausea and vomiting, two common side effects that accompany chemotherapy in cancer patients. Most non-THC plant cannabinoids e.g. cannabidiol and cannabigerol, seem to be devoid of psychotropic properties. However, the precise pathways through which these molecules produce an antitumor effect have not yet been fully characterized. We therefore investigated the antitumor and anti-inflammatory activities of cannabidiol (CBD) in human prostate cancer cell lines LNCaP, DU145, PC3, and assessed whether there is any advantage in using cannabis extracts enriched in cannabidiol and low in THC. Results obtained in a panel of prostate cancer cell lines clearly indicate that cannabidiol is a potent inhibitor of cancer cell growth, with significantly lower potency in non-cancer cells. The mRNA expression level of cannabinoid receptors CB1 and CB2, vascular endothelial growth factor (VEGF), PSA (prostate specific antigen) are significantly higher in human prostate cell lines. Treatment with Cannabis extract containing high CBD down regulates CB1, CB2, VEGF, PSA, pro-inflammatory cytokines/chemokine IL-6/IL-8. Our overall findings support the concept that cannabidiol, which lacks psychotropic activity, may possess anti-inflammatory property and down regulates both cannabinoid receptors, PSA, VEGF, IL-6 and IL-8. High CBD cannabis extracts are cytotoxic to androgen responsive LNCaP cells and may effectively inhibit spheroid formation in cancer stem cells. This activity may contribute to its anticancer and chemosensitizing effect against prostate cancer. Cannabidiol and other non-habit forming cannabinoids could be used as novel therapeutic agents for the treatment of prostate cancer.

The Endocannabinoid System: A Target for Cancer Treatment

“…Furthermore, these effects are mediated by the modulation of the ERK and AKT signaling pathways [90]. CBD (at 0.5-7 µl/mL) inhibits the spheroid formation and dow-nregulates CB1 and CB2 receptors, VEGF, PSA, and pro-inflammatory cytokines IL-6/IL-8 in LNCaP prostate cancer stem cells [91]. In vivo, CBD-enriched cannabis extract (1-100 mg/kg −1 ) reduced tumor size in LNCaP-xenografted mice and enhanced the anticancer effect of bicalutamide (50 mg/kg −1 ), but not of docetaxel (5 mg/kg −1 ), while in DU-145 xenografts CBD was inactive alone but able to potentiate the effect of docetaxel [92].…”

Cannabinoids in cancer treatment: Therapeutic potential and legislation

“…In addition to THC, CBD is another plant-derived cannabinoid that has been extensively studied for its potential antitumor effects [39,[65][66][67][68]. In a panel of human prostate cancer cell lines, Sharma et al [67] showed that CBD is a potent inhibitor of cancer cell growth, while this potency was significantly lower in non-cancer cells.…”

Medicinal plants: used in Anti-cancer treatment

“…The result showed that prostate cancer cell lines clearly indicate that cannabidiol is a potent inhibitor of cancer cell growth with significantly lower potency in noncancer cells. The mRNA expression level of cannabinoid receptors CB1 and CB2, vascular endothelial growth factor (VEGF), PSA (prostate specific antigen) are significantly higher in human prostate cell lines [33].…”