Introduction: In the last two decades, cannabinoids have been studied extensively for their potential use in various fields of medicine including oncology. Aggressive B-cell lymphoma or non-Hodgkin lymphoma (NHL) is the fifth leading cause of human cancer death and is the second fastest growing cancer with regard to mortality in people. Lymphomas are generally characterized by a high rate of initial remission following conventional CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based therapies; however, 30% of humans will succumb to drug-resistant relapse. To date, lymphoma is still a serious condition for which there are unmet medical needs. The purpose of this study was to demonstrate the antitumor effects of cannabinoids in B-cell lymphoma using canine as a model due to striking similarities b/w canines and human B-cell lymphoma in histology, biology, and gene expression. Another advantage of studying B-cell lymphoma in canines will be to study a spontaneous tumor in future clinical trials instead of using genetically engineered animal models of cancer.
Methodology: Canine B-cell lymphoma cell lines (1771, CLBL1) and lymphocytes from healthy dogs (control) were cultured in RPMI. Expression of cannabinoid receptors was studied using qPCR. Based on receptor expression 17-71 cells were treated with receptor agonists (AEA, 2AG, CBD, THC, WIN, and HU-210,) and antagonists (S16 and S28); normal lymphocytes were treated with CBD. Cell viability was assessed using MTT assay. Biochemical analysis was performed using spectrofluorometry to evaluate apoptotic makers involved in inducing cell death. Data were analyzed using ordinary one-way ANOVA on Prism software.
Results: All B-cell lymphoma cell lines showed positive expression of CB1 and CB2 receptors. Cell viability assay demonstrated a dose-dependent decrease in cell proliferation with all cannabinoid receptor agonists. Out of two antagonists used, S28 did not affect cell proliferation; however, S16 showed antiproliferative effects like agonists. No significant effect on cell proliferation was found on normal lymphocytes. Biochemical analysis showed a decrease in nitrite and caspase activity in treated cells as compared to control untreated cells.
Conclusion: Canine lymphoma cells express both cannabinoid receptors like human B-cell lymphoma, and activating cannabinoid receptors with agonists induces cancer cell death in canine B-cell lymphoma. Our results suggest that cannabinoids have an antiproliferative and proapoptotic effect on canine lymphoma cells and support the need for further studies providing evidence of efficacy against both human and canine B-cell lymphomas.
Acknowledgments: We are grateful to Dr. Steven Suter, North Carolina State University, for sharing canine lymphoma cell lines.
Citation Format: Saba Omer, Dawn Boothe, Mohammedohammed Mansour, Muralikrishnan Dhanasekaran, Satyanarayana Pondugula. Antitumor effects of cannabinoids against B-cell lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-28.