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Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer

Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and inva...

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Autores principales: Jeng, Kuo-Shyang, Jeng, Chi-Juei, Sheen, I-Shyan, Wu, Szu-Hua, Lu, Ssu-Jung, Wang, Chih-Hsuan, Chang, Chiung-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983844/
https://www.ncbi.nlm.nih.gov/pubmed/29734730
http://dx.doi.org/10.3390/ijms19051375
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author Jeng, Kuo-Shyang
Jeng, Chi-Juei
Sheen, I-Shyan
Wu, Szu-Hua
Lu, Ssu-Jung
Wang, Chih-Hsuan
Chang, Chiung-Fang
author_facet Jeng, Kuo-Shyang
Jeng, Chi-Juei
Sheen, I-Shyan
Wu, Szu-Hua
Lu, Ssu-Jung
Wang, Chih-Hsuan
Chang, Chiung-Fang
author_sort Jeng, Kuo-Shyang
collection PubMed
description Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells.
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spelling pubmed-59838442018-06-05 Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer Jeng, Kuo-Shyang Jeng, Chi-Juei Sheen, I-Shyan Wu, Szu-Hua Lu, Ssu-Jung Wang, Chih-Hsuan Chang, Chiung-Fang Int J Mol Sci Article Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells. MDPI 2018-05-05 /pmc/articles/PMC5983844/ /pubmed/29734730 http://dx.doi.org/10.3390/ijms19051375 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeng, Kuo-Shyang
Jeng, Chi-Juei
Sheen, I-Shyan
Wu, Szu-Hua
Lu, Ssu-Jung
Wang, Chih-Hsuan
Chang, Chiung-Fang
Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title_full Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title_fullStr Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title_full_unstemmed Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title_short Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer
title_sort glioma-associated oncogene homolog inhibitors have the potential of suppressing cancer stem cells of breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983844/
https://www.ncbi.nlm.nih.gov/pubmed/29734730
http://dx.doi.org/10.3390/ijms19051375
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