Antimetastatic effect of epigenetic drugs, hydralazine and valproic acid, in Ras-transformed NIH 3T3 cells
Por:
Perez-Cardenas, Enrique, Taja-Chayeb, Lucia, Trejo-Becerril, Catalina, Chanona-Vilchis, Jose, Chavez-Blanco, Alma, Dominguez-Gomez, Guadalupe, Langley, Elizabeth, Garcia-Carranca, Alejandro, Duenas-Gonzalez, Alfonso
Publicada:
1 ene 2018
Resumen:
Introduction: Metastasis involves the accumulation of genetic and
epigenetic alterations leading to activation of prometastatic genes and
inactivation of antimetastatic genes. Among epigenetic alterations, DNA
hypermethylation and histone hypoacetylation are the focus of intense
translational research because their pharmacological inhibition has been
shown to produce antineoplastic activity in a variety of experimental
models.
Aims: This study aimed to evaluate the antimetastatic effect of the
DNA-methylation inhibitor, hydralazine, and the histone deacetylase
inhibitor, valproic acid.
Methods: NIH 3T3-Ras murine cells were treated with hydralazine and
valproic acid to evaluate their effects upon cell proliferation, cell
motility, chemotaxis, gelatinase activity, and gene expression. Lung
metastases were developed by intravenous injection of NIH 3T3-Ras cells
in BALB/c nu/nu mice and then treated with the drug combination.
Results: Treatment induced a growth-inhibitory effect on NIH 3T3-Ras
cells, showed a trend toward increased gelatinase activity of MMP2 and
MMP9, and inhibited chemotaxis and cell motility. The combination led to
a strong antimetastatic effect in lungs of nude mice.
Conclusion: Hydralazine and valproic acid, two repositioned drugs as
epigenetic agents, exhibit antimetastatic effects in vitro and in vivo
and hold potential for cancer treatment.
Filiaciones:
Perez-Cardenas, Enrique:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Taja-Chayeb, Lucia:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Trejo-Becerril, Catalina:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Chanona-Vilchis, Jose:
Inst Nacl Cancerol, Dept Pathol, Mexico City, DF, Mexico
Chavez-Blanco, Alma:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Dominguez-Gomez, Guadalupe:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Langley, Elizabeth:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Garcia-Carranca, Alejandro:
Univ Nacl Autonoma Mexico, Unit Biomed Res Canc, Biomed Res Inst, Mexico City, DF, Mexico
Inst Nacl Cancerol, Unit Biomed Res Canc, Mexico City, DF, Mexico
Duenas-Gonzalez, Alfonso:
Univ Nacl Autonoma Mexico, Unit Biomed Res Canc, Biomed Res Inst, Mexico City, DF, Mexico
Inst Nacl Cancerol, Unit Biomed Res Canc, Mexico City, DF, Mexico
|