Curcumin induces cell death without oligonucleosomal DNA fragmentation in quiescent and proliferating human CD8+ cells.
Cytotoxic CD8+ cells play an important role in determining host response to tumor, thus chemotherapy is potentially dangerous as it may lead to T cells depletion. The purpose of this study was to elucidate the propensity of quiescent and proliferating human CD8+ cells to undergo cell death upon treatment with curcumin, a natural dye in Phase I of clinical trials as a prospective chemopreventive agent.


METHODS
We treated human quiescent or proliferating CD8+ cells with 50 microM curcumin or irradiated them with UVC. Cell death symptoms such as decreased cell viability, chromatin condensation, activation of caspase-3 and specific DFF40/CAD endonuclease and oligonucleosomal DNA fragmentation were analyzed using MTT test, microscopic observation, Western blotting and flow cytometry.


RESULTS
Curcumin decreased cell viability, activated caspase-3 and decreased the level of DFF45/ICAD, the inhibitor of the DFF40/CAD endonuclease. However, this did not lead to oligonucleosomal DNA degradation. In contrast, UVC-irradiated proliferating, but not quiescent CD8+ cells revealed molecular and morphological changes characteristic for apoptosis, including oligonucleosomal DNA fragmentation. Curcumin can induce cell death in normal human lymphocytes both quiescent and proliferating, without oligonucleosomal DNA degradation which is considered as a main hallmark of apoptotic cell death. Taking into account the role of CD8+ cells in tumor response, their depletion during chemotherapy could be particularly undesirable.
Magalska
Adriana
A
Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, Warszawa, Poland.
Brzezinska
Agnieszka
A
Bielak-Zmijewska
Anna
A
Piwocka
Katarzyna
K
Mosieniak
Grazyna
G
Sikora
Ewa
E
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D003851:Deoxyribonucleases / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin