natriuretic-peptide--brain and Carcinoma--Small-Cell

Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer.. These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h.. Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells.. Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Blotting, Western; Carcinoma, Small Cell; Cell Proliferation; Humans; Lung Neoplasms; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Protein Precursors

The tumoral production of brain natriuretic peptide (BNP) was studied using 9 small cell lung cancer (SCLC) cell lines which were established from patients with small cell lung cancer. BNP cDNA fragment was generated from 20 microg total RNA which was prepared from the human right cardiac atrium by reverse transcription-based polymerase chain reaction. Expression of BNP mRNA was detected in 30 microg total cellular RNA from these cell lines by RNase protection assays in 5 of 9 SCLC cell lines. Radioimmunoassays using 125I-radiolabeled human BNP(1-32) and antihuman BNP(1-32) antibody detected immunoreactivity in cell pellets from SCLC cell lines which had detectable BNP mRNA. BNP immunoreactivity in the cell pellets corresponds with the data from BNP mRNA analyses. We conclude that SCLC cells have detectable BNP mRNA by RNase protection assay and BNP immunoreactivity in the cells.

Topics: Carcinoma, Small Cell; DNA Primers; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Natriuretic Peptide, Brain; Polymerase Chain Reaction; Radioimmunoassay; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured