Acute lymphoblastic leukemia (ALL) and lymphoma are aggressive hematological malignancies originating from immature lymphoid cells. These disorders are characterized by rapid uncontrolled proliferation and impaired differentiation, leading to disruption of normal hematopoiesis and immune function. Despite significant advancements in treatment strategies, including chemotherapy, immunotherapy, and targeted therapies, relapse and resistance remain major clinical challenges [1]. Investigating alternative therapies for ALL and lymphoma is crucial because they may offer new, less toxic treatment options for patients who experience severe side effects from conventional therapies. Additionally, exploring these alternatives could lead to novel mechanisms of action that improve treatment outcomes and enhance patients’ quality of life.
In this study, ALL and lymphoma cells were treated with CBD to evaluate its therapeutic effects. ALL and lymphoma cell lines Jurkat, UoC-B6, RAJI, NALM-6, REH, and SU-DHL-4 were treated with 16 μM CBD. Cell viability and apoptosis were evaluated using trypan blue exclusion for live/dead cell counting and propidium iodide (PI) staining analyzed by flow cytometry to assess apoptosis. RT-qPCR was performed to quantify gene expression levels of target genes. Results demonstrated that CBD treatment significantly increased cell apoptosis, upregulateds immune-regulatory genes such as TNFα and IL-6, and downregulated epigenetic regulators DNMT1 and HDAC1 in ALL and lymphoma cells. The downregulation of epigenetic regulatory enzymes DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) implicates epigenetic modulation as a mechanism underlying CBD’s anti-proliferative effects. Further gene expression analysis revealed upregulation of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6), suggesting activation of immune-modulatory pathways.
These findings suggest a multifaceted mechanism of action for CBD, modulating both proliferation and epigenetic regulation. Our results highlight the need for further research into CBD as an alternative or adjunct therapy for ALL, aiming to improve patient outcomes by reducing chemotherapy-related side effects and overcoming drug resistance. Exploring novel treatment strategies such as CBD-based therapies may offer new hope for patients with refractory or relapsed disease.