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

研究成果: 雜誌貢獻文章

摘要

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.

原文英語
文章編號110808
頁(從 - 到)110808
期刊Food and Chemical Toxicology
133
DOIs
出版狀態已發佈 - 十一月 1 2019

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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    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