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.
Highlights
Carnosine (β‐alanyl‐L‐histidine) is a natural dipeptide that is found in muscle and brain tissue, especially in lean beef, fish and chicken [1]
The mRNA expression of β‐catenin and transcription factor 4 (Tcf‐4), two key molecules in cell proliferation‐associated signaling, was decreased after HCT‐116 cells were treated with carnosine
When HCT‐116 cells were treated with carnosine, ATP levels were significantly decreased and reactive oxygen species (ROS) levels and mixed lineage kinase domain‐like protein (MLKL) mRNA expression were significantly increased
Summary
Carnosine (β‐alanyl‐L‐histidine) is a natural dipeptide that is found in muscle and brain tissue, especially in lean beef, fish and chicken [1]. Previous studies have shown that carnosine has a number of physiological effects, including antiaging effects [2], cerebral protection [3], antioxidation [4], inhib‐ iting inflammation [5], reducing Parkinson's disease [6] and inhibiting metastasis [7,8]. Carnosine has been shown to inhibit the proliferation of human gastric carcinoma cells by regulating Akt and mammalian target of rapamycin (mTOR) signaling [9]. Carnosine will be reacted to anserine and ophidine. These reactions lead to methylhistidine formation, which is an important indicator of muscle breakdown [10]. The hydrolysis of carnosine produces histidine and β‐alanine. Lee et al [13] show that carnosine can induce apop‐ tosis and cell cycle arrest to lead to reduced cell viability in human colorectal HCT‐116 cells. The investigation of carnosine‐mediated suppression of cell proliferation and induction of cell growth in human colorectal cells is remains an important issue
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