Induction of apoptosis by type Iβ protein kinase G in the human breast cancer cell lines MCF-7 and MDA-MB-468.

Abstract

Activation of protein kinase G (PKG) by cyclic guanosine 3,5-monophosphate (cGMP) has become of considerable interest as a novel molecular approach for the induction of apoptosis in cancer cells. This study was conducted to investigate the role of PKG isoforms in the regulation of cell growth in human breast cancer cell lines MCF-7 and MDA-MB468. The expression levels of PKG isoforms were also examined using real-time reverse transcriptase polymerase chain reaction. No differences in the gene expression of PKG isoforms were observed between MCF-7 and MDA-MB-468 cells. To investigate the effects of PKG isoforms on the regulation of cell growth, the cGMP analogues 8-APT-cGMP (PKGIα activator), 8-Br-PET-cGMP (PKGIβ activator) and 8-pCPT-cGMP (PKGII activator) were employed. Apoptosis was assessed with the Annexin-V-propidium iodide (PI) staining, cell cycle analysis and caspase-3/9 activity assay. Treatment of MCF-7 and MDA-MB-468 cells with 8-Br-PET-cGMP resulted in a concentration-dependent cell growth inhibition and apoptosis, whereas neither PKGIα nor PKGII activators had any effect on the cell growth. The role of PKGIβ in the inhibition of cell growth was confirmed using PKGI and PKGII inhibitors. The present study is the first to demonstrate the involvement of PKGIβ in the inhibition of cell growth and induction of apoptosis in breast cancer cells.

• Authors: Faranak Fallahian, Fatemeh Karami-Tehrani, Siamak Salami
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 30 Issue 3 Pg. 183-90 (Apr 2012) ISSN: 1099-0844 [Electronic] England
• PMID: 22095901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Cyclic GMP-Dependent Protein Kinase Type I
• Cyclic GMP-Dependent Protein Kinases
• PRKG1 protein, human
• Caspase 3
• Caspase 8
• Cyclic GMP

Topics

• Apoptosis
• Breast Neoplasms (enzymology, genetics, pathology)
• Caspase 3 (genetics, metabolism)
• Caspase 8 (genetics, metabolism)
• Cell Cycle
• Cell Line, Tumor
• Cell Proliferation
• Cyclic GMP (analogs & derivatives, metabolism)
• Cyclic GMP-Dependent Protein Kinase Type I
• Cyclic GMP-Dependent Protein Kinases (genetics, metabolism)
• Female
• Humans