title: [Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].
abstract: OBJECTIVE
  To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms.
  
  
  METHODS
  Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR.
  
  
  RESULTS
  TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres.
  
  
  CONCLUSIONS
  TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. E-mail: penglisky@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Fu-Xi
authors.initials: FX
authors.lastname: Li
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Shao
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Xiong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051927:CD24 Antigen; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D006877:Hydroxamic Acids; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; C012589:trichostatin A