title: Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines.
abstract: The 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. 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.
authors.affiliation: Department of Clinical Biochemistry, Cancer Research Laboratory, School of Medical Science, Tarbiat Modares University, Tehran, Iran.
authors.forename: Faranak
authors.initials: F
authors.lastname: Fallahian
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Karami-Tehrani
authors.forename: Siamak
authors.initials: S
authors.lastname: Salami
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aghaei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006162:Guanylate Cyclase / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D007527:Isoenzymes; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D017869:Cyclic GMP-Dependent Protein Kinases; C506433:CASP9 protein, human; D053453:Caspase 9; D006162:Guanylate Cyclase; D006152:Cyclic GMP