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KMID : 0350519950480041083
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Journal of Catholic Medical College
1995 Volume.48 No. 4 p.1083 ~ p.1097
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The Apotosis Induced by all-trans Retinoic Acid in Acute Promyelocytic Leukemia Cell Line (HL-60)
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Abstract
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The acute promyelocytic HL-60 cell line can be induced to apoltosis in response to a variety of chemical stimuli. We have found that all-trans retinoic acid (ATRA), cytosine arabinoside (AraC) and cycloheximide (CHX) treatment into HL-60 cells
over
a
period of 7 days result in a progresive increase in the proportion of cells with mature neutrophil morphologies, which was closely followed by an increase in the proportion of cells exhibiting the morphological characteristics of apoptosis, the
non-pathological mode of cell death.
@EN The results were as follows :
@EN 1. When HL-60 cells were incubated with 0.1, 1, 5 and 10μM/ml of ATRA for 3 days, the viability of cells was decreased with increment of ATRA dose.
2. When HL-60 cells were incubated with 2μM/ml of ATRA daily for 1, 3, 7 days, the viability of the cells was decreased with increment daily dose of ATRA.
3. When HL-60 cells were incubatfed with 1μM/ml of ATRA and 0.1, 1, 10㎍/ml of Ara-C for 3 days, the viability of cells was decreased with increment of Ara-C dose.
4. When HL-60 cells were incubated for 7 days with 50 ㎍/ml of CHX and 2μM/ml of ATRA daily for 1, 3 and 7 days, the viability of cells was decreased with increment daily dose of ATRA.
5. When the medium containing HL-60 cells added by 2μM/ml of ATRA daily for 1, 3, and 7 days, the expression of bcl-2 protein was decreased and the expression of c-myc protein was increased with increment of ATRA dose.
These results suggested that the exposure of human myeloid leukemia HL-60 cells to ATRA, Ara-C and CHX produced intfernuclesomal DNA fragmentation of approximately 200 base pair multiples, and the morphologic changes were characteristic of cells
undergoing apoptosis. ATRA plus Ara-C induced apoptosis was associated with a marked inhibition of suspension culture growth and clonogenic survival of HL-60 cells. In addition, Atra treatement decreased bcl-2 oncogene expression, which is known
to
block apoptosis. The exposure of ATRA increased c-myc oncogene expression moderately. These findings indicated that ATRA might induce leukemic cell death by gene directed mechanism of apoptosis.
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