[Effects of hexamethylene bisacetamide on cell cycle and expression of its regulatory proteins in HL-60 cells].
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.
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China. qinhong-wang@yahoo.com.cn
Qin-Hong
QH
Wang
Yi
Y
Xie
Hua-Hua
HH
Fan
Li
L
Gao
Yan
Y
Liu
D000081:Acetamides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D056741:Cyclin D; D019927:Cyclin E / Q000032:analysis; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D019942:Genes, p16; D018922:HL-60 Cells; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics
D000081:Acetamides; D000970:Antineoplastic Agents; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D056741:Cyclin D; D019927:Cyclin E; D050762:Cyclin-Dependent Kinase Inhibitor p15; D016213:Cyclins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C014026:hexamethylene bisacetamide