Leptin OB3 peptide suppresses leptin-induced signaling and progression in ovarian cancer cells

J Biomed Sci. 2017 Jul 27;24(1):51. doi: 10.1186/s12929-017-0356-6.


Background: Obesity and its comorbidities constitute a serious health burden worldwide. Leptin plays an important role in diet control; however, it has a stimulatory potential on cancer cell proliferation. The OB3 peptide, a synthetic peptide, was shown to be more active than leptin in regulating metabolism but with no mitogenic effects in cancer cells.

Methods: In this study, we investigated the proliferative effects, gene expressions and signaling pathways modulated by leptin and OB3 in human ovarian cancer cells. In addition, an animal study was performed.

Results: Leptin, but not OB3, induced the proliferation of ovarian cancer cells. Interestingly, OB3 blocked the leptin-induced proliferative effect when it was co-applied with leptin. Both leptin and OB3 activated the phosphatidylinositol-3-kinase (PI3K) signal transduction pathway. In addition, leptin stimulated the phosphorylation of signal transducer and activator of transcription-3 (STAT3) Tyr-705 as well as estrogen receptor (ER)α, and the expression of ERα-responsive genes. Interestingly, all leptin-induced signal activation and gene expressions were blocked by the co-incubation with OB3 and the inhibition of extracellular signal-regulated kinase (ERK)1/2. Coincidently, leptin, but not OB3, increased circulating levels of follicle-stimulating hormone (FSH) which is known to play important roles in the initiation and proliferation of ovarian cancer cells.

Conclusions: In summary, our findings suggest that the OB3 peptide may prevent leptin-induced ovarian cancer initiation and progression by disrupting leptin-induced proliferative signals via STAT3 phosphorylation and ERα activation. Therefore, the OB3 peptide is a potential anticancer agent that might be employed to prevent leptin-induced cancers in obese people.

Keywords: Leptin; OB3-leptin peptide; Obesity; Ovarian cancer.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leptin / genetics*
  • Leptin / metabolism*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / physiopathology*
  • Peptide Fragments / metabolism*
  • Signal Transduction / genetics*


  • Leptin
  • Peptide Fragments
  • leptin (116-130)