title: Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors.
abstract: SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies.
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000, China. Electronic address: zouzhengzhi@m.scnu.edu.cn.
authors.forename: Zhengzhi
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang 471000, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Luo
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510000, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Nie
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Xiamen Cancer Center, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Geng
authors.affiliation: Xiamen Cancer Center, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China. Electronic address: myjgj_77@163.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Mi
mesh_terms: D000072283:A549 Cells; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D056921:Nuclear Receptor Coactivator 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3
keywords: AKT; Apoptosis; Bcl-2; Cancer; HDAC; SRC-3