Effects of 17-DMAG on diffuse large B-cell lymphoma cell apoptosis.

ABSTRACT

17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) is a water soluble, semisynthetic derivative of endotoxin that has anticancer effects. The aim of the present study was to determine whether 17-DMAG enhances the apoptosis of lymphoma cells in diffuse large B-cell lymphoma. Apoptosis was induced in SU-DHL-4 diffuse large B-cell lymphoma cells treated with 17-DMAG, as evaluated by MTT assay and flow cytometry analysis. Apoptosis-associated protein levels were assessed using western blotting, and the results indicated that B-cell lymphoma 2 (Bcl-2)-associated protein X (Bax) was upregulated, whereas heat shock protein family A member 5 (HSPA5) and Bcl-2 were downregulated. Additionally, staining with 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide revealed that treatment with 17-DMAG decreased mitochondrial membrane potential in SU-DHL-4 diffuse large B-cell lymphoma cells. These results suggested that 17-DMAG is able to inhibit proliferation in diffuse large B-cell lymphoma cells in a concentration-dependent manner. The underlying mechanism may be that 17-DMAG induces oxidative stress, which inhibits the expression of HSPA5 and Bcl-2 and promotes the expression of Bax, leading to the apoptosis of SU-DHL-4 cells. Taken together, these results indicated that 17-DMAG may be an effective novel agent for the treatment of diffuse large B-cell lymphoma.