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l-carnosine induces apoptosis/cell cycle arrest via suppression of NF-κB/STAT1 pathway in HCT116 colorectal cancer cells

  • Jooyeon Lee
  • Jeong-Ran Park
  • Hanbyeol Lee
  • Soojin Jang
  • Se-Min Ryu
  • Hyejin Kim
  • Donguk Kim
  • Aera JangEmail author
  • Se-Ran YangEmail author
Article
  • 272 Downloads

Abstract

l-carnosine, a dipeptide of the amino acids β-alanine and histidine, is found in various tissues, such as the central nervous system and skeletal muscles. Recently, l-carnosine has been reported to possess anti-tumor activity; however, the molecular mechanism underlying its activity in colorectal cancer is still unknown. Therefore, we investigated the effect of l-carnosine using a human colorectal cancer cell line, HCT116. Treatment with l-carnosine (0, 100, or 200 mM) for 24 h gradually reduced cellular proliferation according to immunochemistry and 7-aminoactinomycin D (7-AAD) analyses and induced G0/G1 phase arrest. In the RT-PCR analysis, l-carnosine decreased the mRNA levels of cell cycle-related genes in HCT116 cells. In the Western blot analysis, levels of the cyclin D1, BAX/Bcl-2, cleaved caspase-3, p21, and p53 proteins were significantly increased in cells treated with l-carnosine. We next determined whether STAT1/NF-κB pathway is involved in regulation of cell cycle arrest- and cell death-associated gene in HCT116. The l-carnosine treatment significantly inhibited the phosphorylation of STAT1 on Tyr701 and NF-κB p65 on Ser276 and Ser536, and then, we exogenously blocked the NF-κB phosphorylation using Bay 11-7082. Based on our findings, l-carnosine induces cell cycle arrest and apoptosis in human colorectal cancer cells by suppressing of NF-κB/STAT1 signaling.

Keywords

l-carnosine Colorectal cancer Apoptosis Cell cycle arrest NF-κB p65 STAT1 

Notes

Acknowledgements

This work was supported by 2015 Hanwoo Board.

Supplementary material

11626_2018_264_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 13 kb)

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Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  • Jooyeon Lee
    • 1
  • Jeong-Ran Park
    • 1
  • Hanbyeol Lee
    • 1
  • Soojin Jang
    • 1
  • Se-Min Ryu
    • 1
  • Hyejin Kim
    • 2
  • Donguk Kim
    • 2
  • Aera Jang
    • 2
    Email author
  • Se-Ran Yang
    • 1
    Email author
  1. 1.Department of Thoracic and Cardiovascular SurgeryKangwon National UniversityChuncheonSouth Korea
  2. 2.Department of Animal Products and Food ScienceKangwon National UniversityChuncheonSouth Korea

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