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

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


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.

MeSH terms

  • Adipocytes / physiology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Leptin / administration & dosage
  • Leptin / pharmacology
  • Leptin / physiology*
  • Male
  • Mitogen-Activated Protein Kinases / physiology
  • Obesity / complications*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphorylation
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / pathology*
  • Risk Factors
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Leptin
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases