Leptin-derived peptides block leptin-induced proliferation by reducing expression of pro-inflammatory genes in hepatocellular carcinoma cells

Yih Ho, Shwu Huey Wang, Yi Ru Chen, Zi Lin Li, Yu Tang Chin, Yu Chen S.H. Yang, Yun Hsuan Wu, Kuan Wei Su, Hung Ru Chu, Hsien Chung Chiu, Dana R. Crawford, Ya Jung Shih, Patricia Grasso, Heng Yuan Tang, Hung Yun Lin, Paul J. Davis, Jacqueline Whang-Peng, Kuan Wang

Research output: Contribution to journalArticle

Abstract

The obesity-regulated gene, leptin, is essential for diet. Leptin resistance causes obesity and related diseases. Certain types of diet are able to decrease leptin resistance. However, leptin has been shown to be correlated with inflammation and stimulate proliferation of various cancers. Two synthetic leptin derivatives (mimetics), OB3 and [D-Leu-4]-OB3, show more effective than leptin in reducing obesity and diabetes in mouse models. OB3 inhibits leptin-induced proliferation in ovarian cancer cells. However, effects of these mimetics in hepatocellular carcinoma (HCC) have not been investigated. In the present study, we examined the effects of OB3 and [D-Leu-4]-OB3 on cell proliferation and gene expressions in human HCC cell cultures. In contrast to what was reported for leptin, OB3 and [D-Leu-4]-OB3 reduced cell proliferation in hepatomas. Both OB3 and [D-Leu-4]-OB3 stimulated expression of pro-apoptotic genes. Both compounds also inhibited expressions of pro-inflammatory, proliferative and metastatic genes and PD-L1 expression. In combination with leptin, OB3 inhibited leptin-induced cell proliferation and expressions of pro-inflammation-, and proliferation-related genes. Furthermore, the OB3 peptide inhibited phosphoinositide 3-kinase (PI3K) activation which is essential for leptin-induced proliferation in HCC. These results indicate that OB3 and [D-Leu-4]-OB3 may have the potential to reduce leptin-related inflammation and proliferation in HCC cells.

Original languageEnglish
Article number110808
Pages (from-to)110808
JournalFood and Chemical Toxicology
Volume133
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • Hepatocellular carcinoma cells
  • Inflammation
  • Leptin
  • OB3 peptide
  • Obesity

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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  • Cite this

    Ho, Y., Wang, S. H., Chen, Y. R., Li, Z. L., Chin, Y. T., Yang, Y. C. S. H., Wu, Y. H., Su, K. W., Chu, H. R., Chiu, H. C., Crawford, D. R., Shih, Y. J., Grasso, P., Tang, H. Y., Lin, H. Y., Davis, P. J., Whang-Peng, J., & Wang, K. (2019). Leptin-derived peptides block leptin-induced proliferation by reducing expression of pro-inflammatory genes in hepatocellular carcinoma cells. Food and Chemical Toxicology, 133, 110808. [110808]. https://doi.org/10.1016/j.fct.2019.110808