Radiosensitization of cervical cancer cells with epigenetic drugs hydralazine and valproate.
OBJECTIVE
To evaluate the radiosensitizing effects of the DNA methylation inhibitor hydralazine in combination with valproic acid, a histone deacetylase inhibitor in cervical cancer cells.


METHODS
Cell viability assays were performed in the SiHa cervical cancer cell line treated with hydralazine and valproic acid for five days with and without cisplatin. Cell irradiation was performed using teletherapy (1.25 MV).


RESULTS
Neither hydralazine, valproic acid or cisplatin as single agents increased the cytotoxicity from radiation, however, the combination of hydralazine with valproic acid at ten microM and one mM, respectively, did induce radiosensitization (p = 0.046). Interestingly, this effect was further increased with the triple combination of hydralazine, valproic acid, and cisplatin (p = 0.041), where cell viability decreased more than 50% as compared to radiation alone.


CONCLUSIONS
The present results demonstrate that epigenetic drugs increase the efficacy of cisplatin chemoradiation in cervical cancer cells.
E
E
Mani
L A
LA
Medina
K
K
Isaac-Olivé
A
A
Dueñas-González
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011878:Radiotherapy; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D014635:Valproic Acid / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents; D006830:Hydralazine; D014635:Valproic Acid; D015254:DNA Modification Methylases