Hexamethylene bisacetamide (
HMBA) is referred as a differentiation-inducer for the clinical treatment of
acute myeloid leukemia and
myelodysplastic syndrome. However, the molecular mechanism of the effects of
HMBA on myeloid leukemic cells remains unknown. In this study, the effects of
HMBA on cell cycle and expression of
cell cycle regulatory proteins in HL-60 cell were investigated in order to explore its pharmacological mechanism. The altered distribution of cell cycle and expression of its regulatory
proteins (
cyclin D,
cyclin E and p27) in HL-6 0 cell induced by
HMBA were analyzed by flow cytometry. The effects on transcription for
mRNA of CKI p15, p16 and p27 in HL-60 cell were further studied by RT-PCR. The results showed that
HMBA could mainly commit HL-60 cell to G0/G1 arrest and the significantly decreased endocytic
cyclin E protein and increased
cyclin D/p27
protein after
HMBA treatment were found. There was no expression of p15, p16
mRNA in untreated HL-60 cell and 3 mmol/L of
HMBA could make them expressed after exposed for 24 h or 48 h respectively. The expression of p27
mRNA was positive and no obviously different in untreated HL-60 cells exposed for 24 h, 48 h and 72 h. These results suggested that one of the pharmacological mechanisms of
HMBA was to elevate the expression of p27 and reduce the
cyclin E expression as well as to activate the expression of p15, p16 gene
mRNA, that arrested cell at G0/G1 and exerted its effects of anti-proliferation.