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Breast cancer is the most common cause of cancer and the second most common cause of death in women worldwide.
Despite major recent advances in therapy, more effective approaches to the treatment and prevention are necessary.
Histone deacetylase inhibitors (HDACIs) provide an alternative therapeutic approach for the treatment of breast cancer.
The therapeutic potential of HDACIs stems from their capacity to selectively induce apoptosis in tumor cells. HDACIs show
promise as a single anti-cancer drugthat given the range of molecular and biological responses andhave a minimal toxicity to
normal cells. In the present study, we investigated and compared the anticancer effects of two structurally distinct HDACIs,
Vorinostat (SAHA) and Valproic Acid (VPA) respectively. In addition, we tested the effect of VPA/SAHA as a combination
treatment, using T-47Dhuman breast cancer cell line. Anticancer effects of tested drugs were assessed by MTT assay, western
blotting analysis of expression levels of p53, β-catenin and cyclin D1. In addition, apoptotic induction and morphological
characteristics of T-47D breast cancer cells upon treatment with SAHA, VPA and combined treatment byboth drugs were
performed.Furthermore, the antitumor effect of SAHA was investigatedbyimmunohistochemical analysis to detectcyclin Dl
expression in tumor tissues of MNU-induced breast carcinoma in vivo. In vivo model, breast tumor size was decreased and
nuclear localization of cyclin D1profoundly was changedupon SAHA treatment. In vitro, SAHAshowed a strong inhibitory
effect on cyclin D1 expression compared to VPAinT-47D cells. In addition, HDACIs- treated T-47D cancer cells suppressed
the expression level of oncogenic β-catenin expression and enhancedtotal p53 expression. Furthermore, SAHA,VPA and VPA/
SAHA combined treatments induced morphological changes, apoptosis induction and DNA fragmentations. These results
suggest that the combination treatment of SAHA and/or VPA exerts significant antitumor activity and could be a promising
therapeutic candidate for human breast cancer treatment.
Soha M H is a lecturer assistant at the biochemistry department-Faculty of Science - Alexandria University, Egypt.
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