Rapamycin and curcumin induce apoptosis in primary resting B chronic lymphocytic leukemia cells.
B chronic lymphocytic leukemia (B-CLL) cells exist in patients as slowly accumulating resting as well as proliferating B cells. In this study, we examined whether Rapamycin and Curcumin, two naturally occurring compounds shown to have apoptotic effects, could selectively induce apoptosis in resting B-CLL cells. Mononuclear cells isolated from patients with B-CLL were treated with these agents and analysed by AnnexinV/propidium iodide binding, caspase activity, and changes in bcl-2/Bax ratio. Rapamycin and curcumin significantly induced apoptosis in resting B-CLL cells obtained from patients with CLL. Furthermore, rapamycin and curcumin increased caspase 9, 3 and 7 activity, decreased anti-apoptotic bcl-2 levels, and increased the pro-apoptotic protein Bax. These data suggest rapamycin and curcumin may be an effective treatment for B-CLL and are of high clinical significance considering the growing population of patients and lack of efficient treatment for this malignant disease.
The Mina and Everard Goodman Faculty of Life Sciences, Safdie Institute for AIDS and Immunology Research, Bar-Ilan University, Ramat-Gan, Israel.
Rami
R
Hayun
Eitan
E
Okun
Alain
A
Berrebi
Lev
L
Shvidel
Lucette
L
Bassous
Benjamin
B
Sredni
Uri
U
Nir
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D003474:Curcumin; D020123:Sirolimus