Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell lines

Objective. Although responsive to first-line treatments, follicular lymphoma (FL) remains a fatal disease of increasing worldwide incidence. In efforts to find novel approaches to inhibit proliferation and induce apoptosis in FL cells, we examined the action of naturally occurring compound curcumin in the three recently established FL cell lines. Materials and Methods. Cytotoxic effects and determination of apoptotic attributes upon curcumin treatment were analyzed using growth inhibition, [H-3]-thymidine, fluorescence microscopy, and flow cytometry assays, as well as Western blotting. Chemical inhibitor studies for the assessment of caspase and cathepsin contribution were applied. Expression of 10 members of the bcl-2 family proteins was evaluated by immunoblotting. Results. Curcumin inhibited proliferation and growth, and induced profound apoptosis associated with a shift in the balance of the bcl-2 family proteins, in all cell lines tested. Strikingly, we observed that curcumin-induced caspase-dependent apoptosis is also associated with lysosomal rupture (1,MP). An increase in intracellular ROS generation appeared critical for curcumin-evoked LMP, loss of Delta psi(m). caspase activation, and cell death, as well as ascorbic acid-mediated enhancement of curcumin's action. Conclusion. We have demonstrated for the first time that curcumin is an efficient inducer of apoptosis in FL cell lines, meriting its further evaluation in vivo. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.