[Effect of sodium butyrate in combination with ATRA on the proliferation/differentiation of MDS cell line SKM-1].
The study was purposed to explore the molecular mechanisms of sodium butyrate (NaB) action on SKM-1 cell proliferation/differentiation and to study its synergistic effect with all-trans retinoic acid (ATRA). SKM-1 cells were grown in the absence or presence of NaB and/or ATRA; the percentage of viable cells was determined by trypan blue exclusion; differentiation was investigated by nitro-blue tetrazolium (NBT) reduction; adhesion molecules of cell surface were analysed by FACS; cell cycle distribution was studied after DNA staining by propidium iodide; D-type cyclins, CDK and P21 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that NaB and/or ATRA blocked cells mainly in the G0/G1 phase of the cell cycle; ATRA inhibited the mRNA expression of CDK6, CDK4, cyclin D3 and cyclin D1; NaB inhibited the mRNA expression of CDK2, cyclin D2 and cyclin D1; ATRA and NaB inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclin D1, cyclin D2 and cyclin D3; ATRA and/or NaB both stimulated p21 expression at the mRNA levels. It is concluded that the NaB effect on cell proliferation/differentiation may be linked to its ability to induce expression of p21 mRNA and inhibit the cyclin D-CDK complexes. These observations support the claim that NaB has the synergistic effect with ATRA.
Li
Chun-Rui
CR
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Liu
Wen-Li
WL
Huang
Mei
M
Deng
Jin-Niu
JN
Sun
Han-Ying
HY
Zhou
Jian-Feng
JF
D000368:Aged; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D006801:Humans; D008297:Male; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*
D002087:Butyrates; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D014212:Tretinoin