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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.
PMID
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Authors

Mayor MeshTerms
Keywords

Actinomycin D

SOX2

breast cancer

cancer stem cells

tumoroids

Journal Title anticancer research
Publication Year Start




PMID- 28373426
OWN - NLM
STAT- MEDLINE
DA  - 20170404
DCOM- 20170413
LR  - 20170413
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 37
IP  - 4
DP  - 2017 Apr
TI  - Actinomycin D Down-regulates SOX2 Expression and Induces Death in Breast Cancer
      Stem Cells.
PG  - 1655-1663
AB  - BACKGROUND/AIM: 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.
      MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
CI  - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Das, Tuhin
AU  - Das T
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
FAU - Nair, Rajesh R
AU  - Nair RR
AD  - Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Transgenex Nanobiotech Inc., Tampa, FL, U.S.A.
FAU - Green, Ryan
AU  - Green R
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Center for Research and Education in Nanobioengineering, University of South
      Florida, Tampa, FL, U.S.A.
FAU - Padhee, Shruti
AU  - Padhee S
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Transgenex Nanobiotech Inc., Tampa, FL, U.S.A.
AD  - Center for Research and Education in Nanobioengineering, University of South
      Florida, Tampa, FL, U.S.A.
FAU - Howell, Mark
AU  - Howell M
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Center for Research and Education in Nanobioengineering, University of South
      Florida, Tampa, FL, U.S.A.
FAU - Banerjee, Jit
AU  - Banerjee J
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A.
FAU - Mohapatra, Shyam S
AU  - Mohapatra SS
AD  - Departments of Internal Medicine, University of South Florida, Tampa, FL, U.S.A.
AD  - Center for Research and Education in Nanobioengineering, University of South
      Florida, Tampa, FL, U.S.A.
AD  - James A. Haley VA Hospital, Tampa, FL, U.S.A.
FAU - Mohapatra, Subhra
AU  - Mohapatra S
AD  - Department of Molecular Medicine, University of South Florida, Tampa, FL, U.S.A. 
      [email protected]
AD  - Center for Research and Education in Nanobioengineering, University of South
      Florida, Tampa, FL, U.S.A.
AD  - James A. Haley VA Hospital, Tampa, FL, U.S.A.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (RNA, Messenger)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 1CC1JFE158 (Dactinomycin)
SB  - IM
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Breast Neoplasms/drug therapy/metabolism/*pathology
MH  - Cell Proliferation/drug effects
MH  - Dactinomycin/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Neoplastic Stem Cells/drug effects/metabolism/*pathology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - SOXB1 Transcription Factors/*antagonists & inhibitors/genetics/metabolism
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - *Actinomycin D
OT  - *SOX2
OT  - *breast cancer
OT  - *cancer stem cells
OT  - *tumoroids
EDAT- 2017/04/05 06:00
MHDA- 2017/04/14 06:00
CRDT- 2017/04/05 06:00
PHST- 2017/01/12 [received]
PHST- 2017/03/09 [revised]
PHST- 2017/03/13 [accepted]
AID - 37/4/1655 [pii]
AID - 10.21873/anticanres.11496 [doi]
PST - ppublish
SO  - Anticancer Res. 2017 Apr;37(4):1655-1663.

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