Apoptosis of mink lung epithelial cells by co-treatment of low-dose staurosporine and transforming growth factor-β1 depends on the enhanced TGF-β signaling and …

EM Ju, KC Choi, SH Hong, CH Lee, BC Kim… - Biochemical and …, 2005 - Elsevier
EM Ju, KC Choi, SH Hong, CH Lee, BC Kim, SJ Kim, IH Kim, SH Park
Biochemical and biophysical research communications, 2005Elsevier
We demonstrate how co-treatment of low-dose staurosporine (STS) and TGF-β1, which
alone have little effect on cell death, markedly induces apoptosis in Mv1Lu mink lung
epithelial cells, but not in its clonal variant R1B cells lacking functional TGF-β signaling. This
process was associated with mitochondria-dependent apoptosis and the enhanced TGF-
β/Smad signaling in Mv1Lu cells. When R1B cells were infected with adenovirus carrying
wild-type ALK5, a functional TGF-β type I receptor gene, the apoptotic cell death was …
We demonstrate how co-treatment of low-dose staurosporine (STS) and TGF-β1, which alone have little effect on cell death, markedly induces apoptosis in Mv1Lu mink lung epithelial cells, but not in its clonal variant R1B cells lacking functional TGF-β signaling. This process was associated with mitochondria-dependent apoptosis and the enhanced TGF-β/Smad signaling in Mv1Lu cells. When R1B cells were infected with adenovirus carrying wild-type ALK5, a functional TGF-β type I receptor gene, the apoptotic cell death was significantly restored in these cells following co-treatment of low-dose STS and TGF-β1. Treatment of Mv1Lu cells with both low-dose STS and TGF-β1 decreased the activity of phospho-Akt, which is involved in cell survival signal. In addition, pre-treatments of PI3 kinase inhibitors, LY294002 and wortmannin, further increased the apoptosis of MvlLu cells induced by co-treatment of low-dose STS and TGF-β1. And overexpression of constitutively active Akt (myr-Akt) using adenoviral expression system inhibited the apoptotic cell death of Mv1Lu cells by about 50% upon co-treatment of low-dose STS and TGF-β1. These results suggest that co-treatment of low-dose STS and TGF-β1 induces apoptosis of mink lung epithelial cells by enhancing TGF-β signaling and in part suppressing cytoprotective signaling.
Elsevier