Inhibition of phospholipase D2 augments histone deacetylase inhibitor-induced cell death in breast cancer cells.

BACKGROUND: Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their effect on tumor treatment has been disappointing mainly due to the acquisition of HDAC inhibitor resistance. However, the mechanisms underlying such resistance remain unclear. METHODS: In this study, we performed Western blot, q-PCR, and promoter assay to examine the expression of HDAC inhibitor-induced phospholipase D2 (PLD2) in MDA-MB231and MDA-MB435 breast cancer cells. Apoptosis and proliferation were analyzed by flow cytometry. In addition to invasion and migration assay, angiogenesis was further measured using in vitro tube formation and chick embryo chorioallantoic membrane model. RESULTS: HDAC inhibitors including suberoylanilide hydroxamic acid (SAHA), trichostatin, and apicidin, induce expression of PLD2 in a transcriptional level. SAHA upregulates expression of PLD2 via protein kinase C-ζ in breast cancer cells and increases the enzymatic activity of PLD. The combination treatment of SAHA with PLD2 inhibitor significantly enhances cell death in breast cancer cells. Phosphatidic acid, a product of PLD activity, prevented apoptosis promoted by cotreatment with SAHA and PLD2 inhibitor, suggesting that SAHA-induced PLD2 expression and subsequent activation of PLD2 might confers resistance of breast cancer cells to HDAC inhibitor. The combinational treatment of the drugs significantly suppressed invasion, migration, and angiogenesis, compared with that of either treatment. CONCLUSION: These findings provide further insight into elucidating the advantages of combination therapy with HDAC and PLD2 inhibitors over single-agent strategies for the treatment of cancer.

Macro-Level Factors & their Influence on Family Perceptions in Two Cultures / Factores macro y su influencia en las percepciones familiares en dos culturas

Values, political beliefs, and family perceptions are sensitive to cultural change, which embraces change in the political, economic, and other societal-level spheres. This study investigated the impact of culture-level individualism and gender on family perceptions and the interrelations between the macro-level and individual level factors in South Korea and Hungary, two countries that have undergone recent social change. The study included data from 288 university students. Cultural and gender influences on Postmodernist values, democratic beliefs, political interest, political conservatism, perceptions of family relatedness and democratisation were found, and the overall model of interrelations between all the variables was tested using SEM (structural equation modelling) analysis.

Los valores, creencias políticas y percepciones familiares son sensibles a los cambios culturales, los cuales implican modificaciones en las esferas política, económica y a otros niveles sociales. Este estudio investigó el impacto del nivel de individualismo cultural y el género en las percepciones familiares y en las inter-relaciones entre factores de nivel macro e individual en Corea del Sur y Hungría, dos países que han experimentado cambios sociales recientes. Este estudio incluyó los datos de 288 estudiantes universitarios. Se encontraron influencias culturales y del género en los valores post-modernistas, creencias democráticas, intereses políticos, conservadurismo político, percepciones de la conexión familiar y la democratización. Para probar el modelo general de relaciones entre todas las variables se usó el análisis de Ecuaciones Estructurales.