Glioma-associated oncogene homolog inhibitors have the potential of suppressing cancer stem cells of breast cancer

Kuo Shyang Jeng, Chi Juei Jeng, I. Shyan Sheen, Szu Hua Wu, Ssu Jung Lu, Chih Hsuan Wang, Chiung Fang Chang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1375
JournalInternational journal of molecular sciences
Volume19
Issue number5
DOIs
Publication statusPublished - May 5 2018
Externally publishedYes

Keywords

  • Breast carcinoma
  • GANT-58
  • Gli-1
  • HPI-1
  • Sonic hedgehog signaling pathway

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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