Summary
To explore the molecular mechanisms of sodium butyrate working 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 sodium butyrate and/or ATRA. The percentage of viable cells was determined by trypan blue exclusion. Differentiation was dtermined by nitroblue tetrazolium (NBT) reduction and cell surface adhesion molecules was analyzed by FACS. Cell cycle distribution was examined after DNA staining by propidium iodide. D-type cyclins, cdks and P21 mRNA were studied by reverse transcription-polymerase chain reaction. Our results showed that sodiun butyrate and/or ATRA blocked cells mainly in the G0/G1 phase of the cell cycle. ATRA inhibited the mRNA expression of CDK6, CDK4, cyclinD3 and cyclinD1. Sodium butyrate inhibited the mRNA expression of CDK2, cyclinD2 and cyclinD1. ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Both ATRA and/or sodium butyrate stimulated p21 expression at the mRNA levels Our results suggest that the effect of sodium butyrate on cell proliferation/differentiation might be linked to its ability to induce expression of p21 mRNA and inhibit the cyclin-cdk complexes. Our observations support the notion that the sodium butyrate works synergistically with ATRA.
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References
Silverman L R Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS). Oncologist, 2001. 6 Suppl 5: 8
Kizaki M, Koeffler H P. Differentiation-inducing agents in the treatment of myelodysplastic syndromes. Semin Oncol, 1992; 19: 95
Butler L M, Agus D B, Scher H Iet al. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cellsin vitro andin vivo. Cancer Res, 2000, 60(18): 5165
Nakagawa T, Matozaki S, Murayama Tet al. Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome Br J Haematol, 1993, 85(3): 469
Du C, Redner R L, Cooke M Pet al. Overexpression of wild-type retinoic acid receptor a (RARa) recapitulates retinoic acid-sensitive transformation of primary myeloid progenitors by acute promyelocytic leukemia RARa-fusion genes. Blood, 1999, 94: 793
Redner R L, Wang J and Liu J M. Chromatin remodelling and leukemia: new therapeutic paradigms. Blood, 1999, 94: 417
Xu L, Glass C K, Rosenfeld M G. Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet, 1999, 9: 140
Hodin R A, Meng S, Archer Set al. Cellular growth state differentially regulates enterocyte gene expression in butyrate-treated HT-29 cells. Cell Growth Differ. 1996, 7: 647.
Harper J W, Elledge S J, Keyomarsi Ket al. Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell. 1995, 6: 387.
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HUANG Mei, female, born in 1971, Doctor in Charge
This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30070326).
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Mei, H., Wenli, L., Chunrui, L. et al. The effect of sodium butyrate in combination with ATRA on the proliferation/differentiation of SKM-1. Current Medical Science 24, 334–337 (2004). https://doi.org/10.1007/BF02861861
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DOI: https://doi.org/10.1007/BF02861861