title: The enhanced antiproliferative response to combined treatment of trichostatin A with raloxifene in MCF-7 breast cancer cells and its relevance to estrogen receptor β expression.
abstract: Antiestrogen is one type of the endocrine therapeutic agents for estrogen receptor α (ERα)-positive breast cancer. Unfortunately, this treatment alone is insufficient. Here we reported a novel potential anticancer strategy by using histone deacetylase (HDAC) inhibitor to enhance the action of endocrine therapy in ERα-positive breast cancer cell. The well-described HDAC inhibitor, trichostatin A (TSA), and antiestrogen raloxifene were found to, respectively, inhibit E2-induced proliferation of MCF-7 breast cancer cell in a dose-responsive and time-dependent manner. TSA and raloxifene enhanced the antiproliferative activity of each other by promoting cell death via apoptosis and cell cycle arrest. Thus, they displayed better antiproliferative effects in combined treatment than that with either agent alone. The expression level of estrogen receptor β (ERβ) showed a marked increase after TSA or/and raloxifene treatment. Treatments with TSA or/and raloxifene resulting in the up-regulation of ERβ are in accordance with the antiproliferative effects of the two agents. Furthermore, the over-expression of ERβ by adenovirus delivery could inhibit the proliferation of MCF-7 tumor cells and drastically enhanced the antiproliferative effects of TSA and raloxifene. These results demonstrated that the interference of ERβ on the antiproliferative effects of HDAC inhibitor and antiestrogen constitutes a promising approach for breast cancer treatment.
authors.affiliation: Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Tu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Junmei
authors.initials: J
authors.lastname: Tian
authors.forename: Walter
authors.initials: W
authors.lastname: Akers
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D016203:CDC2 Protein Kinase; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019926:Cyclin B; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006877:Hydroxamic Acids; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases