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

Yu Tang Chin, Le Ming Wang, Meng Ti Hsieh, Ya Jung Shih, André Wendindondé Nana, Chun A. Changou, Yu Chen S.H. Yang, Hsien Chung Chiu, Earl Fu, Paul J. Davis, Heng Yuan Tang, Hung Yun Lin

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number51
JournalJournal of Biomedical Science
Volume24
Issue number1
DOIs
Publication statusPublished - Jul 27 2017

Keywords

  • Leptin
  • OB3-leptin peptide
  • Obesity
  • Ovarian cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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    Chin, Y. T., Wang, L. M., Hsieh, M. T., Shih, Y. J., Nana, A. W., Changou, C. A., Yang, Y. C. S. H., Chiu, H. C., Fu, E., Davis, P. J., Tang, H. Y., & Lin, H. Y. (2017). Leptin OB3 peptide suppresses leptin-induced signaling and progression in ovarian cancer cells. Journal of Biomedical Science, 24(1), [51]. https://doi.org/10.1186/s12929-017-0356-6