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 induce anti-leptin-related inflammation and proliferation in HCC cells.

Original languageEnglish
Article number110808
JournalFood and Chemical Toxicology
Volume133
DOIs
Publication statusPublished - Nov 1 2019

Fingerprint

leptin (116-130)
hepatoma
Leptin
leptin
Hepatocellular Carcinoma
Genes
Cells
peptides
Peptides
genes
cells
Cell proliferation
cell proliferation
obesity
Obesity
inflammation
Cell Proliferation
Nutrition
Inflammation
Diet

Keywords

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

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Leptin-derived peptides block leptin-induced proliferation by reducing expression of pro-inflammatory genes in hepatocellular carcinoma cells. / Ho, Yih; Wang, Shwu Huey; Chen, Yi Ru; Li, Zi Lin; Chin, Yu Tang; Yang, Yu Chen S.H.; Wu, Yun Hsuan; Su, Kuan Wei; Chu, Hung Ru; Chiu, Hsien Chung; Crawford, Dana R.; Shih, Ya Jung; Grasso, Patricia; Tang, Heng Yuan; Lin, Hung Yun; Davis, Paul J.; Whang-Peng, Jacqueline; Wang, Kuan.

In: Food and Chemical Toxicology, Vol. 133, 110808, 01.11.2019.

Research output: Contribution to journalArticle

Ho, Yih ; Wang, Shwu Huey ; Chen, Yi Ru ; Li, Zi Lin ; Chin, Yu Tang ; Yang, Yu Chen S.H. ; Wu, Yun Hsuan ; Su, Kuan Wei ; Chu, Hung Ru ; Chiu, Hsien Chung ; Crawford, Dana R. ; Shih, Ya Jung ; Grasso, Patricia ; Tang, Heng Yuan ; Lin, Hung Yun ; Davis, Paul J. ; Whang-Peng, Jacqueline ; Wang, Kuan. / Leptin-derived peptides block leptin-induced proliferation by reducing expression of pro-inflammatory genes in hepatocellular carcinoma cells. In: Food and Chemical Toxicology. 2019 ; Vol. 133.
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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 induce anti-leptin-related inflammation and proliferation in HCC cells.",
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AU - Ho, Yih

AU - Wang, Shwu Huey

AU - Chen, Yi Ru

AU - Li, Zi Lin

AU - Chin, Yu Tang

AU - Yang, Yu Chen S.H.

AU - Wu, Yun Hsuan

AU - Su, Kuan Wei

AU - Chu, Hung Ru

AU - Chiu, Hsien Chung

AU - Crawford, Dana R.

AU - Shih, Ya Jung

AU - Grasso, Patricia

AU - Tang, Heng Yuan

AU - Lin, Hung Yun

AU - Davis, Paul J.

AU - Whang-Peng, Jacqueline

AU - Wang, Kuan

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N2 - 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 induce anti-leptin-related inflammation and proliferation in HCC cells.

AB - 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 induce anti-leptin-related inflammation and proliferation in HCC cells.

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KW - Leptin

KW - OB3 peptide

KW - Obesity

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