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

In Vitro Cell Dev Biol Anim. 2018 Aug;54(7):505-512. doi: 10.1007/s11626-018-0264-4. Epub 2018 Jun 4.


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: Apoptosis; Cell cycle arrest; Colorectal cancer; L-carnosine; NF-κB p65; STAT1.

MeSH terms

  • Apoptosis / drug effects*
  • Carnosine / pharmacology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • G1 Phase / drug effects
  • HCT116 Cells
  • Humans
  • Models, Biological
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Resting Phase, Cell Cycle / drug effects
  • STAT1 Transcription Factor / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tumor Suppressor Protein p53
  • Carnosine