Synthesis, Characterization, and in vitro Experiments of Saturated Cannabinoids on Pancreatic Ductal Adenocarcinoma Cell Lines (HPAF-II, MIA-PaCa2, ASPC-1, and PANC-1)

Abstract

Introduction: Cannabinoid receptors CB1 and CB2 are the primary endogenous receptors with which cannabinoids interact, inducing a variety of physiological and psychological effects. Although interactions with other receptors such as TRPV1 and GPCR55 have been recognized, these interactions may contribute significantly to cancer remediation by modulating internal cellular pathways. The main active constituents in the cannabis plant, cannabidiol (CBD) and tetrahydrocannabinol (THC), have been characterized as non-intoxicating with potential medical benefits or intoxicating with debated benefits, respectively. Nevertheless, cannabinoids have demonstrated efficacy as single-agent treatments for certain diseases. Objectives: This study focuses on in-vitro cytotoxicity screening of rare cannabinoids and their synthetic analogs. Methods: The synthetic derivatives of THC and tetrahydrocannabivarin (THCV) were screened in in vitro MTT assay for their potential as antineoplastic agents against pancreatic cancer cell lines (MIA-PaCa2, HPAF-II, ASPC-1 and PANC-1). Results: The saturated products derived from THC and THCV have shown substantially lower IC50 values than the parent compounds and as compared to poly(ADP-ribose) polymerase (PARP) inhibitors, Olaparib and Veliparib. Conclusion: The data collected suggest that these rare saturated cannabinoids may have promising activity comparable to or surpassing standard anticancer agents such as poly(ADP-ribose) polymerase (PARP) inhibitors.