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.
Hayun
Rami
R
The Mina and Everard Goodman Faculty of Life Sciences, Safdie Institute for AIDS and Immunology Research, Bar-Ilan University, Ramat-Gan, Israel.
Okun
Eitan
E
Berrebi
Alain
A
Shvidel
Lev
L
Bassous
Lucette
L
Sredni
Benjamin
B
Nir
Uri
U
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