Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines

Oncology
E ShimizuS Sone

Abstract

The retinoblastoma gene product (RB protein) plays a key role in the progression of the cell cycle from G1 to S phase in normal and neoplastic cells. The activity of RB is regulated by phosphorylation and dephosphorylation with cell-cycle-dependent protein kinases. We investigated the effect of the protein kinase inhibitors, staurosporine and 7-hydroxy-staurosporine (UCN-01), on RB protein expression of N417 small cell lung cancer cells (absent RB), H209 small cell lung cancer cells (mutant RB), and Ma-31 non-small cell lung cancer cells (wild-type RB), using immunologic blotting. Staurosporine and UCN-01 each suppressed the growth of N417, H209 and Ma-31 cells in a dose-dependent manner in MTT assay. IC50 values of staurosporine for N417, H209 and Ma-31 cells were 54, 29 and 602 nM, respectively. IC50 values of UCN-01 for N417, H209 and Ma-31 cells were 737, 181 and 2,197 nM, respectively. Exposure to staurosporine and UCN-01 for 72 h each suppressed the level of expression and altered the ratio of phosphorylated/dephosphorylated RB protein (ppRB/pRB) of Ma-31 cells. Conversely, these agents increased the expression level of RB protein at concentrations less than IC50, and did not change phosphorylation status of mutant RB pro...Continue Reading

Citations

Dec 5, 2003·European Journal of Biochemistry·Silvia PeñuelasCarlos J Ciudad
Dec 12, 2003·Clinical Lung Cancer·Adrian M Senderowicz
Jun 5, 2007·Critical Reviews in Oncology/hematology·David Michod, Christian Widmann
Apr 9, 2013·Revista Do Instituto De Medicina Tropical De São Paulo·Shailendra Kapoor
Oct 7, 2003·Oncogene·Adrian M Senderowicz
Jul 23, 1999·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·V Yerly-MottaP Hervé
Nov 11, 1998·General Pharmacology·A Gescher

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