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DNA甲基化抑制剂肼苯哒嗪和组蛋白脱乙酰酶抑制剂丙戊酸对癌细胞系的抗肿瘤作用。

Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines.

作者信息

Chavez-Blanco Alma, Perez-Plasencia Carlos, Perez-Cardenas Enrique, Carrasco-Legleu Claudia, Rangel-Lopez Edgar, Segura-Pacheco Blanca, Taja-Chayeb Lucia, Trejo-Becerril Catalina, Gonzalez-Fierro Aurora, Candelaria Myrna, Cabrera Gustavo, Duenas-Gonzalez Alfonso

机构信息

Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.

Division of Clinical Research, Instituto Nacional de Cancerología, Mexico City, Mexico.

出版信息

Cancer Cell Int. 2006 Jan 31;6:2. doi: 10.1186/1475-2867-6-2.

DOI:10.1186/1475-2867-6-2
PMID:16448574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1408081/
Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

在癌症发生的表观遗传改变中，DNA高甲基化和组蛋白低乙酰化是深入研究的焦点，因为它们的药理学抑制作用已在多种实验模型中显示出抗肿瘤活性。本研究的目的是评估DNA甲基化抑制剂肼屈嗪和组蛋白脱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。

结果

单独使用时，肼屈嗪对宫颈、结肠、乳腺、肉瘤、神经胶质瘤和头颈癌细胞系没有生长抑制作用。相反，丙戊酸显示出强大的生长抑制作用，在某些细胞系中，肼屈嗪可增强这种作用。单独使用时，肼屈嗪和丙戊酸对整体基因过表达表现出不同的作用，但联合处理细胞时，过表达的基因数量增加。用肼屈嗪和丙戊酸处理HeLa细胞可导致吉西他滨、顺铂和阿霉素的细胞毒性增加。当用人纤维肉瘤细胞异种移植的小鼠同时接受肼屈嗪和丙戊酸治疗时，观察到阿霉素具有更高的抗肿瘤作用。

结论

肼屈嗪和丙戊酸分别是用于心血管和神经疾病的两种广泛使用的药物，同时使用时具有有前景的抗肿瘤作用，并且可能会提高当前细胞毒性药物的抗肿瘤疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/68af24dd1658/1475-2867-6-2-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/bf48c1189328/1475-2867-6-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/e8d24e012b6a/1475-2867-6-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/a9ab87cf57ca/1475-2867-6-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/68af24dd1658/1475-2867-6-2-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/bf48c1189328/1475-2867-6-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/e8d24e012b6a/1475-2867-6-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/a9ab87cf57ca/1475-2867-6-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5899/1408081/68af24dd1658/1475-2867-6-2-4.jpg

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