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BJU Int. 2008 Aug;102(3):383-8. doi: 10.1111/j.1464-410X.2008.07534.x. Epub 2008 Mar 13.

Mitogenic and anti-apoptotic actions of adipocyte-derived hormone leptin in prostate cancer cells.

Author information

1
Department of Urology, Helios Clinics Berlin-Buch, University Medical School of Charité, Berlin, Germany. rhoda@ucsd.edu

Abstract

OBJECTIVE:

To investigate the proliferative and anti-apoptotic effects of leptin on human prostate cancer cells, and the role of related signalling pathways in mediating these actions, as obesity is a possible risk factor for prostate cancer and leptin, an adipocyte-derived hormone, has mitogenic action in various cell types.

MATERIALS AND METHODS:

Two human prostate cancer cell lines, DU145 and PC-3, were treated with leptin (5-100 ng/mL) for up to 48 h. Under serum-free conditions, cell proliferation was measured using a colorimetric tetrazolium assay and apoptosis by an enzyme-linked immunosorbent assay measuring cell death. Also, the phosphorylation of ERK1/2 and Akt was detected by Western blotting, and specific inhibitors of mitogen-activated protein kinase (MAPK) (PD98059; 40 microm) and phosphatidylinositol 3-kinase (PI3-K, LY294002; 40 microm) were used to evaluate the role of these signalling pathways.

RESULTS:

Leptin dose-dependently increased the cell number in both cell lines for up to 48 h of incubation, the mean (sem) percentage of the control being 189 (4.3)% for DU145 and 173 (7.5)% for PC-3 (100 ng/mL leptin, 48 h; P < 0.01). Leptin also significantly reduced the number of apoptotic cells after 24 h of treatment, dose-dependently caused ERK1/2 and Akt phosphorylation; pretreatment with inhibitors of MAPK and PI3-K inhibited these responses.

CONCLUSION:

These results show that chronic increases in leptin might enhance the growth of prostate cancer via the MAPK and PI3-K pathways. Further studies are needed to investigate whether the ability of leptin to stimulate mitogenic/anti-apoptotic signal transduction pathways could represent a target for anticancer drug discovery.

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