4.6 Article

Four peptide hormones' specific decrease (up to 97%) of human prostate carcinoma cells

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EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 35, 期 11, 页码 700-710

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BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2362.2005.01569.x

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cancer; cyclic GMP; DNA synthesis; natriuretic peptides; peptide hormones; therapeutics

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Background Mortality from prostate cancer remains a significant problem with current treatment(s), with an expected 30 350 deaths from prostate cancer in 2005. Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide and atrial natriuretic peptide have significant anticancer effects in breast and pancreatic adenocarcinomas. Whether these effects are specific and whether they have anticancer effects in prostate adenocarcinoma cells has not been determined. Materials and methods These peptide hormones were evaluated to determine if they have specific anticancer effects in human prostate adenocarcinomas. Results Dose-response curves revealed a significant (P < 0.05) decrease in human prostate cancer number with each tenfold increase in the concentration from 1 mu M to 1000 mu M (i.e. 1 mM) of these four peptide hormones. There was a 97.4%, 87%, 88% and 89% (P < 0.001 for each) decrease in prostate cancer cells secondary to vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and atrial natriuretic peptide, respectively, at their 1-mM concentrations within 24 h, without any proliferation in the 3 days following this decrease. These same hormones decreased DNA synthesis from 68% to 89% (P < 0.001). When utilized with their respective antibodies their ability to decrease prostate adenocarcinoma cells or inhibit their DNA synthesis was completely blocked. Western blots revealed that for the first time natriuretic peptide receptors (NPR) A- and C- were present in prostate cancer cells. Conclusions These results indicate that these peptide hormones' anticancer effects are specific. Furthermore, they have very potent effects of eliminating up to 97% of prostate cancer cells within 24 h of treatment.

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