The hedgehog (Hh) signaling pathway has been shown to be activated in the cancer stem cells of several
tumor entities. The Hh inhibitor
GDC-0449 has been proven to be effective in some
cancers but not yet in
lung cancer. We aimed at investigating whether
GDC-0449 is effective in the
lung cancer cell lines HCC (
adenocarcinoma) and H1339 (
small-cell-lung carcinoma), whether in these cell lines stem cell-like side populations (SPs) can be identified, and whether possible effects of
GDC-0449 are mediated via SPs. SPs were identified by spectrum shift and decreased fluorescence after staining with 2.5 μg/ml
Hoechst 33342. Expression of
proteins was quantified by immunofluorescence.
GDC-0449 (25 and 50 μM) inhibited concentration-dependent cell growth in HCC and H1339 cells. Further, the inhibitory effects of
cisplatin on cell growth were augmented. In HCC and H1339 cell lines, SPs of 0.57 and 0.46% could be identified, respectively. SP, but not non-SP, cells were able to repopulate the original
tumor population. The Hh
receptor smoothened was detectable in SP but not in non-SP cells, showing the activation of the Hh pathway only in SPs.
GDC-0449 considerably reduced SPs in HCC and H1339 cells. We demonstrate for the first time that
GDC-0449 effectively reduces cell growth in
lung cancer cell lines. This effect is mediated by the inhibition of stem cell-like SPs.