Open Access

Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis

  • Authors:
    • Shu-Ling Hsieh
    • Jia-Huei Li
    • Cheng-Di Dong
    • Chiu-Wen Chen
    • Chih-Chung Wu
  • View Affiliations

  • Published online on: December 9, 2021     https://doi.org/10.3892/ol.2021.13162
  • Article Number: 44
  • Copyright : © Hsieh et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Carnosine (β‑alanyl‑L‑histidine) is found in beef and fish. The present study aimed to investigate the effects of carnosine on the cell proliferation of human colorectal cancer cells. After human colorectal cancer HCT‑116 cells were treated carnosine for 72 or 96 h, the cell proliferation, apoptosis, autophagy, necroptosis, angiogenesis and the expression of related regulatory molecules were detected using MTT assays, fluorescence image analysis and RT‑qPCR in this study. Treatment of HCT‑116 cells with 5, 10 or 15 mM carnosine for 72 or 96 h significantly decreased cell viability (P<0.05). The mRNA expression of β‑catenin and transcription factor 4 (Tcf‑4) was significantly reduced by 15‑23% and 11‑80%, respectively (P<0.05). When HCT‑116 cells were treated with 15 mM carnosine, the mRNA levels of 1A/1B‑light chain 3 and phosphatidylinositol 3‑kinase were significantly increased by 235% and 249%, respectively (P<0.05). The mRNA level of Beclin‑1 and autophagy levels were significantly increased by 137‑141% in HCT‑116 cells treated with 5, 10 or 15 mM carnosine (P<0.05). Carnosine (15 mM) also increased reactive oxygen species levels and mixed lineage kinase domain‑like protein mRNA expression and depleted ATP levels (P<0.05). The angiogenesis‑regulating molecules vascular endothelial growth factor, epidermal growth factor receptor and hypoxia‑inducible factor 1‑α were all significantly decreased by 10 or 15 mM carnosine treatment. These results showed that carnosine could suppress human colorectal cell proliferation by reducing β‑catenin/Tcf‑4 signaling, inducing autophagy and necroptosis and inhibiting angiogenesis. It was demonstrated that carnosine is a potential compound from dietary food for the future clinical treatment and/or prevention of colorectal cancer.
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February-2022
Volume 23 Issue 2

Print ISSN: 1792-1074
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Spandidos Publications style
Hsieh S, Li J, Dong C, Chen C and Wu C: Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis. Oncol Lett 23: 44, 2022
APA
Hsieh, S., Li, J., Dong, C., Chen, C., & Wu, C. (2022). Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis. Oncology Letters, 23, 44. https://doi.org/10.3892/ol.2021.13162
MLA
Hsieh, S., Li, J., Dong, C., Chen, C., Wu, C."Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis". Oncology Letters 23.2 (2022): 44.
Chicago
Hsieh, S., Li, J., Dong, C., Chen, C., Wu, C."Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis". Oncology Letters 23, no. 2 (2022): 44. https://doi.org/10.3892/ol.2021.13162