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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status
PLoS ONE, Volume 8, No. 8, Article e70846, Year 2013
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Description
Isothiocyanates from plants of the order Brassicales are considered promising cancer chemotherapeutic phytochemicals. However, their selective cytotoxicity on liver cancer has been barely researched. Therefore, in the present study, we systematically studied the chemotherapeutic potency of 4-methylthiobutyl isothiocyanate (MTBITC). Selective toxicity was investigated by comparing its effect on liver cancer cells and their chemoresistant subpopulations to normal primary hepatocytes and liver tissue slices. Additionally, in a first assessment, the in vivo tolerability of MTBITC was investigated in mice. Growth arrest at G2/M and apoptosis induction was evident in all in vitro cancer models treated with MTBITC, including populations with cancer initiating characteristics. This was found independent from TP53; however cell death was delayed in p53 compromised cells as compared to wt-p53 cells which was probably due to differential BH3 only gene regulation i. e. Noxa and its antagonist A1. In normal hepatocytes, no apoptosis or necrosis could be detected after repeated administration of up to 50 μM MTBITC. In mice, orally applied MTBITC was well tolerated over 18 days of treatment for up to 50 mg/kg/day, the highest dose tested. In conclusion, we could show here that the killing effect of MTBITC has a definite selectivity for cancer cells over normal liver cells and its cytotoxicity even applies for chemoresistant cancer initiating cells. Our study could serve for a better understanding of the chemotherapeutic properties of isothiocyanates on human liver-derived cancer cells. © 2013 Lamy et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3732292/bin/pone.0070846.s001.doc
Authors & Co-Authors
Lamy, Evelyn
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Hertrampf, Anke
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Germany, Freiburg Im Breisgau
Universität Freiburg
Herz, Corinna
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Schüler, Julia
United States, Wilmington
Charles River Laboratories, Inc.
Erlacher, Miriam
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Bertele, Daniela
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Bakare, A. Adekunle
Nigeria, Ibadan
University of Ibadan
Wagner, Meike
Germany, Mainz
Universitätsmedizin Mainz
Weiland, Timo
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Lauer, Ulrich M.
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Drognitz, Oliver
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Huber, R.
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Rohn, Sascha
Germany, Hamburg
Universität Hamburg
Giesemann, Torsten
United States, Wilmington
Charles River Laboratories, Inc.
Mersch-Sundermann, Volker
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Statistics
Citations: 19
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0070846
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics