Open AccessAnti‐cancer stem cell activity of a hedgehog inhibitor GANT 61 in estrogen receptor‐positive breast cancer cells
Author(s) -
Kurebayashi Junichi,
Koike Yoshikazu,
Ohta Yusuke,
Saitoh Wataru,
Yamashita Tetsumasa,
Kanomata Naoki,
Moriya Takuya
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13205
Subject(s) - estrogen receptor , cell growth , oncogene , cell cycle , cell , cancer research , cancer , apoptosis , cancer stem cell , hedgehog , cancer cell , cell culture , biology , breast cancer , medicine , chemistry , signal transduction , microbiology and biotechnology , biochemistry , genetics
Estradiol (E2) increases not only the cell growth but also the cancer stem cell ( CSC ) proportion in estrogen receptor ( ER )‐positive breast cancer cells. It has been suggested that the non‐canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER ‐positive breast cancer cells. We studied anti‐ CSC activity of a non‐canonical Hh inhibitor GANT 61 in ER ‐positive breast cancer cells. Effects of GANT 61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER ‐positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD 44/ CD 24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT 61 with antiestrogens on the anti‐cell growth and anti‐ CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER ‐positive cell lines. E2 increased the expression levels of glioma‐associated oncogene ( GLI ) 1 and/or GLI 2. GANT 61 decreased the cell growth in association with a G1‐S cell cycle retardation and increased apoptosis. GANT 61 decreased the E2‐induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2‐induced cell growth and CSC proportion. Combined treatments of GANT 61 with antiestrogens additively enhanced anti‐cell growth and/or anti‐ CSC activities in some ER ‐positive cell lines. In conclusion, the non‐canonical Hh inhibitor GANT 61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER ‐positive breast cancer cells. GANT 61 enhanced anti‐cell growth and/or anti‐ CSC activities of antiestrogens in ER ‐positive cell lines.