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.


METHODS
Cytotoxic effects and determination of apoptotic attributes upon curcumin treatment were analyzed using growth inhibition, [(3)H]-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 (LMP). An increase in intracellular ROS generation appeared critical for curcumin-evoked LMP, loss of Deltapsi(m,) caspase activation, and cell death, as well as ascorbic acid-mediated enhancement of curcumin's action.


CONCLUSIONS
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.
Skommer
Joanna
J
Department of Clinical Microbiology, University of Kuopio, Finland. joannaskommer@yahoo.com
Wlodkowic
Donald
D
Pelkonen
Jukka
J
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014815:Vitamins; D020169:Caspases; D003474:Curcumin; D001205:Ascorbic Acid