Antineoplastic Properties of THCV, HHC and their anti-Proliferative effects on HPAF-II, MIA-paca2, Aspc-1, and PANC-1 PDAC Pancreatic Cell Lines

Cannabinoid receptors CB1 and CB2 are the primary endogenous receptors with which cannabinoids interact, inducing physiological and psychological effects. Although interactions with other receptors including TRPV1 and GPCR55, have been recognized in earlier studies, these interactions may play a significant role in cancer remediation through the unspecified upregulation or downregulation of specific pathways. The main active constituents within the cannabis plant are cannabidiol (CBD) and tetrahydrocannabinol (THC), which have been categorized as either non-intoxicating with benefit or intoxicating with no benefit. These categories are constantly ignored, as cannabinoids have shown efficacy in the treatment of certain diseases and ailments as single-agent compounds. Tetrahydrocannabivarin (THCV), a rare cannabinoid, is a homologue of THC, with the C5 alkyl chain having three carbons rather than the standard five carbon length. THCV has garnered attention in a clinical setting as an anti-obesity drug treating glucose issues. Hexahydrocannabinol (HHC), a hydrogenated analogue of THC, is a rare cannabinoid like THCV. These cyclic cannabinoids are considered rare, because they are typically found in minimal to trace amounts within cannabis sativa and their given C. indica, and C. ruderalis sub species. Increased popularity of these rare cannabinoids has led to proposed experimentation leading to assessing the cytotoxicity of these cannabinoids toward, cancer cells of the pancreas (MIA-PaCa2, HPAF-II, and PANC1). The data evaluated through such studies led to the proposed idea of these rare cyclic cannabinoids towards the treatment of pancreatic cancer due to the modest efficacy as single agent antineoplastics compared to common single agent antineoplastics on the market, with evidence being strongly presented when compared to commercially available anticancer agents poly(ADP-ribose) polymerase (PARP) inhibitors.