Curcumin p38-dependently enhances the anticancer activity of valproic acid in human leukemia cells
Curcumin p38-dependently enhances the anticancer activity of valproic acid in human leukemia cells
复制标题
姜黄素 p38 依赖性增强丙戊酸在人白血病细胞中的抗癌活性。
DOI：
10.1016/j.ejps.2010.06.011
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发表时间：
2010-10-09
影响因子：
4.6
通讯作者：
Wang, Jianmin
中科院分区：
文献类型：
--
作者：
Chen, Jie;Wang, Guiying;Wang, Jianmin
丙戊酸（VPA）是一种广谱组蛋白去乙酰化酶抑制剂，已被用于癌症治疗。近年来，VPA与其他抗癌药物的联合应用被认为是特异性诱导抗癌基因表达的一种有效和必要的策略。姜黄素（Curcumin, Cur）是一种很有前景的天然抗癌药物，可以特异性调节白血病细胞中nf - κ B、bcl-2和bax的表达。然而，VPA与Cur结合的抗癌作用尚未见文献报道。本研究表明，VPA与Cur结合可显著增加Sp1结合、box启动子区域组蛋白H3和H4乙酰化，而bcl-2启动子区域组蛋白H3和H4乙酰化。这特异性上调box表达，导致HL-60细胞增殖阻滞、亚g1 DNA积累和细胞死亡。进一步的研究表明，Cur特异性激活p38 MAPK，这是Sp1在盒子启动子上结合的必要因子。此外，抑制p38 MAPK和敲低box表达均可显著预防VPA和curr诱导的HL-60细胞增殖阻滞和死亡。这些结果表明，Cur可以通过p38依赖性地促进box的表达，从而增强VPA在人白血病细胞中的抗癌活性。(C) 2010 Elsevier B.V.版权所有
Valproic acid (VPA) is a broad-spectrum inhibitor of histone deacetylase, which has been used in cancer therapy. Recently, the combination of VPA with other anticancer agents has been considered as a useful and necessary strategy to specifically induce anticancer gene expression. Curcumin (Cur) is a promising natural anticancer agent that can specifically regulate the expression of NF-kappa B, bcl-2, and bax in leukemia cells. However, no literature is available on the anticancer effects of the combination of VPA and Cur. Here we show that this combination significantly increases Sp1 binding, histone H3 and H4 acetylation in the promoter region of box, but not in that of bcl-2. This specifically up-regulates box expression and leads to HL-60 cell proliferation arrest, sub-G1 DNA accumulation and cell death. Further studies reveal that Cur specifically activates p38 MAPK, an essential factor for Sp1 binding at the box promoter. Moreover, both inhibition of p38 MAPK and knock-down of box expression significantly prevent VPA and Cur-induced proliferation arrest and death in HL-60 cells. These results suggest that Cur could p38-dependently promote box expression and hence enhance the anticancer activity of VPA in human leukemia cells. (C) 2010 Elsevier B.V. All rights reserved.