TAILIEUCHUNG - Báo cáo khoa hoc : Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines

The activation of protein kinase G (PKG) by cyclic guanosine 3,5-mono-phosphate (cGMP) has become of considerable interest as a novel molec-ular approach for the induction of apoptosis in cancer cells. | IFEBS Journal Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines Faranak Fallahian1 Fatemeh Karami-Tehrani1 Siamak Salami2 and Mahmoud Aghaei1 1 Department of ClinicalBiochemistry Cancer Research Laboratory Schoolof MedicalScience Tarbiat Modares University Tehran Iran 2 Department of Biochemistry Schoolof MedicalScience Urmia University of MedicalSciences Iran Keywords apoptosis cyclic guanosine 3 5-monophosphate cGMP MCF-7 MDA-MB-468 protein kinase G Correspondence F. Karami-Tehrani ClinicalBiochemistry Department Schoolof MedicalSciences Tarbiat Modarres University PO Box 14115-331 Tehran Iran Fax 98 21 82884555 Tel 98 21 82883567 E-mail karamitf@ Received 7 March 2011 revised 20 June 2011 accepted 18 July 2011 doi The activation of protein kinase G PKG by cyclic guanosine 3 5-mono-phosphate cGMP has become of considerable interest as a novel molecular approach for the induction of apoptosis in cancer cells. The present study was designed to examine the effects of cGMP and PKG on cell growth and apoptosis in the human breast cancer cell lines MCF-7 and MDA-MB-468. To achieve this 1-benzyl-3- 5P-hydroxymethyl-2P-furyl indazole YC-1 a soluble guanylyl cyclase activator and 8-bromo-cGMP 8-br-cGMP a membrane-permeant and phosphodiesterase-resistant analogue of cGMP were employed in MCF-7 and MDA-MB-468 cells. Then the role of PKG in the induction of apoptosis was evaluated using KT5823 and Rp-8-pCPT-cGMP as specific inhibitors of PKG. The expression of PKG isoforms in these cell lines was also investigated. KT5823 and Rp-8-pCPT-cGMP significantly attenuated the loss of cell viability caused by YC-1 and 8-br-cGMP in these cells. This study provides direct evidence that the activation of PKG by cGMP induces growth inhibition and apoptosis in MCF-7 and MDA-MB-468 breast cancer cell lines. Introduction Cyclic guanosine 3 5 -monophosphate cGMP an ubiquitous

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