Targeting Lymphoma With Benzoxazole Derivatives: Effects on Viability and Protein Expression in Cell Lines

Benzoxazoles possess a wide range of therapeutic activities, including antimicrobial, antitumor, anti-inflammatory, and other. Using in silico and in vitro approaches, we determined the potential antitumor activity of benzoxazoles synthesized from thymoquinone in diffuse large B-cell lymphoma (DLBCL) cells. Molecular docking analysis showed strong binding affinities of benzoxazoles toward Akt and nuclear factor kappa B (NF-κB) protein targets that promote cancer cell proliferation and survival and whose expression is linked to tumorigenesis of activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL subtypes. WST-8 assay showed the highest inhibitory activity of benzoxazole derivative bearing thiophene substituent in both DLBCL models. Western blot analysis indicated the inhibitory activity of selected compounds in HBL-1 cells, with decreased p-NF-κB and p-Akt protein expression, whereas treatment of DHL-4 cells stimulated the expression of p-Akt and p-NF-κB protein levels. These data suggest distinct, cell line-dependent activities of the substances that potentially act through diverse oncogenic signaling pathways in DLBCL cells and activation of compensatory cell mechanisms that could be an important step for combinatorial treatment approaches.