Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines.
Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines.
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DOI：
10.1186/1475-2867-6-2
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发表时间：
2006-01-31
影响因子：
5.8
通讯作者：
Duenas-Gonzalez A
中科院分区：
文献类型：
--
作者：
Chavez-Blanco A;Perez-Plasencia C;Perez-Cardenas E;Carrasco-Legleu C;Rangel-Lopez E;Segura-Pacheco B;Taja-Chayeb L;Trejo-Becerril C;Gonzalez-Fierro A;Candelaria M;Cabrera G;Duenas-Gonzalez A
在癌症发生的表观遗传学改变中，DNA超甲基化和组蛋白低乙酰化是密集研究的重点，因为它们的药理抑制在各种实验模型中都显示出抗肿瘤活性。本研究的目的是评估DNA甲基化抑制剂肼和组蛋白去乙酰酶抑制剂丙戊酸在一组癌细胞系中的联合抗肿瘤作用。联苯肼单独使用时对宫颈、结肠、乳腺、肉瘤、胶质瘤和头颈癌细胞株无生长抑制作用。反之，丙戊酸在某些细胞株中表现出强烈的生长抑制作用，并被肼丙嗪所增强。单独而言，肼和丙戊酸对整体基因的过度表达表现出明显的影响，但当细胞被联合处理时，过度表达的基因数量增加。用肼和丙戊酸处理HeLa细胞后，吉西他滨、顺铂和阿霉素的细胞毒作用增强。阿霉素对人纤维肉瘤细胞移植瘤小鼠有较强的抗肿瘤作用。肼和丙戊酸是两种广泛应用于心血管疾病和神经系统疾病的药物，如果同时使用，可能会增加现有细胞毒药的抗肿瘤效果。
Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid. Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.
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影响因子：
3
作者：
Aparicio, A;Eads, CA;Weber, JS
通讯作者：
Weber, JS
影响因子：
6.4
作者：
Primeau, M;Gagnon, J;Momparler, RL
通讯作者：
Momparler, RL
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
37.3
作者：
Chavez-Blanco A;Segura-Pacheco B;Perez-Cardenas E;Taja-Chayeb L;Cetina L;Candelaria M;Cantu D;Gonzalez-Fierro A;Garcia-Lopez P;Zambrano P;Perez-Plasencia C;Cabrera G;Trejo-Becerril C;Angeles E;Duenas-Gonzalez A
通讯作者：
Duenas-Gonzalez A
影响因子：
11.4
作者：
Krämer, OH;Zhu, P;Göttlicher, M
通讯作者：
Göttlicher, M