Effects of growth hormone-releasing hormone and its agonistic and antagonistic analogs in cancer and non-cancerous cell lines.
The neuropeptide growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and upon the binding to the receptors for GHRH on the pituitary gland regulates the release of growth hormone. Substantial evidence indicate that GHRH, in addition to its physiological role as a hypophysiotrophic hormone, acts as a growth factor in diverse tissues and various tumors. In this study we evaluated the expression of GHRH and its receptors in a variety of cancer and non-cancerous cell lines and studied the effect of GHRH antagonists and agonists on the proliferative cell nuclear antigen, cyclin D3, tumor suppressor protein p53 and carboxyl-terminal-binding protein (CtBP1). Our findings show that GHRH agonist JI-38 downregulates wt-p53 and upregulates the expression of PCNA. GHRH also upregulates CtBP1 protein expression and its antagonists downregulate it in LNCaP prostate cancer cells. Furthermore, GHRH and its agonist JI-38 upregulates the expression of the proliferative markers cyclin D3 and PCNA in A549 non-small cell lung carcinoma and GHRH antagonist MZ-5-156 downregulates it. Our results support previous findings on the mitogenic role of GHRH in cancers and underline the importance of GHRH antagonists as anticancer agents.
Barabutis
Nektarios
N
Research Service (151), Veterans Affairs Medical Center, Miami, FL 33125, USA. nbarabutis@gmail.com
Siejka
Agnieszka
A
Schally
Andrew V
AV
D016475:3T3 Cells; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D056743:Cyclin D3 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D056743:Cyclin D3; D004268:DNA-Binding Proteins; C420262:JI-38; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013007:Growth Hormone-Releasing Hormone; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein