Synthetic Cannabinoid Activity Against Colorectal Cancer Cells

Abstract

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines.Material and Methods: Seven distinct CRC cell lines were treated with 10 μM cannabinoid compounds (from a library of 370 molecules) for 48 h, and cell viability was subsequently measured with MTS assay. Dose–response curves were conducted for compounds that were found to reproducibly reduce cell viability of one or more cell lines.Results: We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines (with an IC50 ≤ 30 μM). Of these compounds, seven were specific for CRC cells, and six were effective in all CRC cell lines tested. Treatment with traditional phytocannabinoids (THC or CBD) was either ineffective or much less potent and only partially efficacious. Treatment with antagonists for the known cannabinoid receptors (alone or in combination) failed to block the activity of the most potent of identified compounds.Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.

The Endocannabinoid System: A Target for Cancer Treatment

“…Interestingly, treatment with ∆9-THC (10 µM) or CBD (10 µM) was either ineffective or much less potent and only partially efficacious. Moreover, treatment with CB1, CB2, GPR55, and/or TRPV1 antagonists (alone or in combination) failed to block the activity of the most potent identified compounds, suggesting that its action is independent of the activation of canonical receptors [54].…”

Loss of p120ctn causes EGFR-targeted therapy resistance and failure

“…The final DMSO concentration was 1% in all conditions. Viability was measured after 48 hours using the MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay (Biovision; Milpitas, CA) [ 35 ].…”

“…For all treatments the final DMSO concentration was 1%. After 48 hours cell viability was assessed using the MTS assay (Biovision; Milpitas, CA) as previously described [ 35 ]. Viability was calculated by normalizing each cell line to vehicle treatment alone.…”

Function of the Endocannabinoid System in Neurodegenerative Diseases and Cancers

“…In vitro and in vivo studies provide evidence that suggests efficacy of cannabinoid agonists in reducing tumor growth and proliferation [19]. Δ 9 -THC has been used as an approved treatment for cancer patients with AIDS experiencing chemotherapy-induced nausea, vomiting, and anorexia [78]. Additionally, cannabinoids have shown to have significant benefit cancer-associated pain and has shown a synergistic effect when combined with opioid analgesics [5].…”

“…Additionally, cannabinoids have shown to have significant benefit cancer-associated pain and has shown a synergistic effect when combined with opioid analgesics [5]. A recent study has identified synthetic cannabinoid compounds that reduce colorectal cancer (CRC) cell viability mediated by an unknown mechanism [78]. American Journal of Plant Sciences Colorectal cancer, the third most common cause of cancer death, is characterized by mutations in the adenomatous polyposis coli (APC), KRAS, and p53 genes [79].…”