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Curcumin abolishes apoptosis resistance of calcitriol‐differentiated HL‐60 cells
Author(s) -
Mosieniak Grazyna,
Sliwinska Malgorzata,
Piwocka Katarzyna,
Sikora Ewa
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.07.038
Subject(s) - apoptosis , curcumin , dna fragmentation , microbiology and biotechnology , programmed cell death , dna damage , etoposide , cellular differentiation , biology , fragmentation (computing) , topoisomerase , apoptotic dna fragmentation , chemistry , cancer research , dna , biochemistry , genetics , ecology , chemotherapy , gene
Exposure of HL‐60 cells to 1,25‐dihydroxyvitamin D 3 (calcitriol) induces their differentiation into monocytes. This terminal differentiation is associated with acquired resistance to many proapoptotic stimuli. Here we show that differentiated HL‐60 cells undergo apoptosis upon curcumin treatment although they retain resistance to apoptosis induced by a topoisomerase poison – etoposide. Curcumin induced changes of nuclear morphology, DNA fragmentation, release of cytochrome c as well as caspase activation in both differentiated and undifferentiated cells. Experiments performed in other laboratories suggested that curcumin initiates apoptosis by DNA damage that results from topoisomerase II poisoning. We measured γH2AX expression, a marker of DNA double strand breaks, in both undifferentiated and differentiated HL‐60 cells treated with curcumin or etoposide. In etoposide‐treated undifferentiated cells early γH2AX expression correlated with initiation phase of apoptosis. In contrast, in curcumin‐treated cells γH2AX expression correlated with apoptotic DNA fragmentation, which is characteristic for the execution phase of apoptosis. Our experiments show that curcumin overcomes the resistance of calcitriol‐differentiated HL‐60 cells to DNA‐damage‐induced apoptosis by activating other cell signaling pathways leading to cell death of HL‐60.