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Histone deacetylase inhibitors (HDACis)\nhave been developed as prospective candidates in anticancer drug development,\nand currently, many of them are under clinical investigation. We assessed the anticancer\nefficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer\ndevelopment and studied its potential mechanisms.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>YF-343 was estimated as a novel HDACi by the HDACi drug screening kit.\nThe biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by\nWestern blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis,\nand induced cell cycle arrest. Furthermore, it also induced autophagy, which plays\na pro-survival role in breast cancer cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly\nsuppressed breast tumor progression as compared to the YF-343 treatment alone\nboth in vitro and in vivo. Mechanistically, the molecular mechanism of YF-343 on autophagy\nwas elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter\ngene assay, chromatin immunoprecipitation assays, immunohistochemical analysis,\nand other methods. E2F7, a transcription factor, promoted the expression of ATG2A\nvia binding to the ATG2A promoter region and then induced autophagy in triple-negative\nbreast cancer cells treated with YF-343.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Our studies have illustrated the mechanisms for potential action of YF-343\non tumor growth in breast cancer models with pro-survival autophagy. The combination\ntherapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867330666230120152815","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T06:28:12Z","timestamp":1674455292000},"page":"4605-4621","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ\nto Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple-\nNegative Breast Cancer"],"prefix":"10.2174","volume":"30","author":[{"given":"Na","family":"Liu","sequence":"first","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-na","family":"Han","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-qi","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-xia","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiran","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Shandong Keyuan Pharmaceutical Co., Ltd, Jinan 251601, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-mei","family":"Wu","sequence":"additional","affiliation":[{"name":"Bureau of Agricultural and Rural Affairs of Laiyang City in Shandong Province, Jinan 265200, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei-fei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.molonc.2010.04.006","volume":"4","author":"Podo F.","year":"2010","unstructured":"Podo F.; Buydens L.M.C.; Degani H.; Hilhorst R.; Klipp E.; Gribbestad I.S.; Van Huffel S.; van Laarhoven H.W.; Luts J.; Monleon D.; Postma G.J.; Schneiderhan-Marra N.; Santoro F.; Wouters H.; Russnes H.G.; S\u00f8rlie T.; Tagliabue E.; B\u00f8rresen-Dale A.L.; Triple-negative breast cancer: present challenges and new perspectives. 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