Effect of sodium butyrate in combination with ATRA on the proliferation/differentiation of MDS cell line SKM-1.
- Author:
Chun-Rui LI
1
;
Wen-Li LIU
;
Mei HUANG
;
Jin-Niu DENG
;
Han-Ying SUN
;
Jian-Feng ZHOU
Author Information
1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
- Publication Type:Journal Article
- MeSH:
Aged;
Butyrates;
pharmacology;
Cell Cycle;
drug effects;
Cell Cycle Proteins;
genetics;
Cell Differentiation;
drug effects;
Cell Line;
Cell Proliferation;
drug effects;
Cyclin D;
Cyclin-Dependent Kinase Inhibitor p21;
Cyclins;
genetics;
Humans;
Male;
Myelodysplastic Syndromes;
pathology;
Reverse Transcriptase Polymerase Chain Reaction;
Tretinoin;
pharmacology
- From:
Journal of Experimental Hematology
2004;12(5):601-605
- CountryChina
- Language:Chinese
-
Abstract:
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.