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In this study, we compared different combinations of HDACIs and anti-cancer agents with anti-angiogenic effects, and analysed their mechanism of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trichostatin A (TSA) and \u03b1-interferon (IFN\u03b1) were the most effective combination across a range of different cancer cell lines, while normal non-malignant cells did not respond in the same manner to the combination therapy. There was a close correlation between absence of basal p21<jats:sup>WAF1<\/jats:sup>expression and response to TSA and IFN\u03b1 treatment. Moreover, inhibition of p21<jats:sup>WAF1<\/jats:sup>expression in a p21<jats:sup>WAF1<\/jats:sup>-expressing breast cancer cell line by a specific siRNA increased the cytotoxic effects of TSA and IFN\u03b1.<jats:italic>In vitro<\/jats:italic>assays of endothelial cell function showed that TSA and IFN\u03b1 decreased endothelial cell migration, invasion, and capillary tubule formation, without affecting endothelial cell viability. TSA and IFN\u03b1 co-operatively inhibited gene expression of some pro-angiogenic factors: vascular endothelial growth factor, hypoxia-inducible factor 1\u03b1 and matrix metalloproteinase 9, in neuroblastoma cells under hypoxic conditions. Combination TSA and IFN\u03b1 therapy markedly reduced tumour angiogenesis in neuroblastoma-bearing transgenic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that combination TSA and IFN\u03b1 therapy has potent co-operative cytotoxic and anti-angiogenic activity. High basal p21<jats:sup>WAF1<\/jats:sup>expression appears to be acting as a resistance factor to the combination therapy.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1476-4598-6-68","type":"journal-article","created":{"date-parts":[[2007,10,25]],"date-time":"2007-10-25T04:39:43Z","timestamp":1193287183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Enhancing the anti-angiogenic action of histone deacetylase inhibitors"],"prefix":"10.1186","volume":"6","author":[{"given":"Selena","family":"Kuljaca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew EL","family":"Tee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Haber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray D","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Dwarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn M","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,10,25]]},"reference":[{"issue":"4","key":"276_CR1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nrd772","volume":"1","author":"RW Johnstone","year":"2002","unstructured":"Johnstone RW: Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. 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