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Butyrate augments interferon-alpha-induced S phase accumulation and persistent tyrosine phosphorylation of cdc2 in K562 cells.

Abstract：

:Interferon-alpha (IFN-alpha) is a clinically useful cytokine for treatment of a variety of cancers, including chronic myelocytic leukaemia (CML). Most CML cells are sensitive to IFN-alpha; however, its biological effects on leukaemic cells are incompletely characterized. Here, we provide evidence that IFN-alpha induces a significant increase in the S phase population in human CML leukaemic cell line, K562, and that the S phase accumulation was augmented by sodium butyrate. In contrast, neither sodium butyrate alone, nor sodium butyrate plus IFN-gamma, affected the cell cycle in K562 cells. These data suggest that the effect of sodium butyrate depended upon IFN-alpha-mediated signalling. The ability of leukaemic cells to exhibit the S phase accumulation after stimulation by IFN-alpha plus sodium butyrate correlated well with persistent tyrosine phosphorylation of cdc2, whereas treatment with IFN-gamma plus sodium butyrate did not affect its phosphorylation levels. Considering that dephosphorylation of cdc2 leads to entry to the M phase, the persistent tyrosine phosphorylation of cdc2 may be associated with the S phase accumulation induced by IFN-alpha and sodium butyrate. In addition, another human CML leukaemic cell line, MEG-01, also showed the S phase accumulation after stimulation with IFN-alpha plus sodium butyrate. Taken together, our studies reveal a novel effect of sodium butyrate on the S phase accumulation and suggest its clinical application for a combination therapy with IFN-alpha, leading to a great improvement of clinical effects of IFN-alpha against CML cells.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Miyachi T,Adachi M,Hinoda Y,Imai K

doi

10.1038/sj.bjc.6690163

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

1018-24

issue

7-8

eissn

0007-0920

issn

1532-1827

journal_volume

79

pub_type

杂志文章

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