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Full Length Research Paper
Effects of valproic acid upon the PI3K/PTEN/AKT pathway in
MCF-7 breast cancer cells
Domínguez-Gómez Guadalupe1, Chavez-Blanco Alma2,
De la Cruz-Hernández Erick2, Díaz-Chávez Jose2,
Gómez-Quiroz Luis E3, Matsumura Pablo3,
Dueñas-Gonzalez Alfonso2
1Programa
de Postgrado en Biología Experimental, Universidad Autónoma
Metropolitana Iztapalapa. México
2Unidad
de Investigación Biomédica en Cáncer, Instituto de
Investigaciones Biomédicas UNAM, Instituto Nacional de
Cancerología, Mexico.3Departamento
de Ciencias de la Salud, División de ciencias Biológicas y
de la Salud, Universidad Autónoma Metropolitana Iztapalapa.
México
*Corresponding Author E-mail:
alfonso_duenasg@yahoo.com
Received 13 March, 2012; Accepted 22 May, 2012
The PI3K/PTEN/AKT pathway plays a key role in breast cancer
progression by stimulating cell proliferation and inhibiting
apoptosis. It has been reported that histone deacetylase (HDAC)
inhibitors induce apoptosis by impeding AKT1 and AKT2
expression or by disrupting HDAC-protein phosphatase 1 (PP1)
complexes. MCF-7 cells were treated with the HDAC inhibitor
valproic acid in order to investigate its effect upon cell
cycle and apoptosis. The levels of total and phosphorylated
PI3K and AKT were determined as well as the interaction
between AKT and PP1 by immunoprecipitation. AKT might also
be regulated by PTEN. Loss of PTEN function results in
constitutive activation of AKT that plays a key role in
tumorigenesis. Therefore, the levels of PTEN and
phosphorylation status were analyzed. The present study
designated that valproic acid induced a marked growth arrest
at both G1 and G2/M and a marked decrease in the phase S.
Furthermore, that histone deacetylase inhibitor, valproic
acid, decreased Akt1 and Akt2 expression, which led to Akt
deactivation and apoptotic cell death. Interestingly, there
was an increase in the activation of PTEN. The results of
the study suggest that valproic acid could be negatively
regulating the pathway PI3K/PTEN/AKT in MCF-7 cells.
Keywords: PI3K, AKT, PTEN, PP1, HDAC, valproic acid.
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