Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells

组蛋白去乙酰化酶抑制剂下调检查点激酶 1 表达,诱导非小细胞肺癌细胞死亡

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作者:William Brazelle, Jenny M Kreahling, Jennifer Gemmer, Yihong Ma, W Douglas Cress, Eric Haura, Soner Altiok

Background

Histone deacetylase inhibitors (HDACis) are promising anticancer drugs; however, the molecular mechanisms leading to HDACi-induced cell death have not been well understood and no clear mechanism of resistance has been elucidated to explain limited efficacy of HDACis in clinical trials.

Conclusions

These results define a pathway through which Chk1 inhibition can mediate HDACi-induced mitotic entry and cell death and suggest that Chk1 could be an early pharmacodynamic marker to assess HDACi efficacy in clinical samples.

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