title: Actinomycin D Down-regulates SOX2 Expression and Induces Death in Breast Cancer Stem Cells.
abstract: One of the major hurdles in the treatment of breast cancers is the inability of anti-cancer drugs to eliminate the breast cancer stem cells (BCSCs) population, which leads to disease relapse. The dearth in anti-cancer drugs that target BCSCs can be attributed to the absence of in vitro screening models that can not only recapitulate the tumor microenvironment consisting of BCSCs but also preserve the 3-dimensional (3D) architecture of in vivo tumors.
  
  
  
  In our present study, we have developed a 3D cell culture system that shows: (i) enrichment of BCSCs, (ii) increased drug resistance, and (iii) generation of hypoxic conditions similar to tumors.
  
  
  
  Using this model, we were able to screen a FDA-approved diversity set and identify as well as validate actinomycin D as a potential anti-breast cancer agent. Interestingly, we show that actinomycin D specifically targets and down-regulates the expression of the stem cell transcription factor, Sox-2. Additionally, down-regulation of Sox-2 leads to depletion of the stem-cell population resulting in the inability of breast cancer cells to initiate tumor progression.
  
  
  
  This study demonstrates the utility of an in vivo-like 3D cell culture system for the identification and validation of anti-cancer agents that will have a better probability of success in the clinic.
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Tuhin
authors.initials: T
authors.lastname: Das
authors.affiliation: Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.|Transgenex Nanobiotech Inc., Tampa, FL, U.S.A.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Nair
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.|Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Ryan
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.|Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.|Transgenex Nanobiotech Inc., Tampa, FL, U.S.A.|Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Shruti
authors.initials: S
authors.lastname: Padhee
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.|Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Mark
authors.initials: M
authors.lastname: Howell
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Jit
authors.initials: J
authors.lastname: Banerjee
authors.affiliation: Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.|Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL, U.S.A.|James A. Haley VA Hospital, Tampa, FL, U.S.A.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Mohapatra
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A. smohapa2@health.usf.edu.|Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL, U.S.A.|James A. Haley VA Hospital, Tampa, FL, U.S.A.
authors.forename: Subhra
authors.initials: S
authors.lastname: Mohapatra
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D003609:Dactinomycin
keywords: Actinomycin D; SOX2; breast cancer; cancer stem cells; tumoroids