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

초록

L-camosine, a dipeptide of the amino acids beta-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-camosine using a human colorectal cancer cell line, HCT116. Treatment with L-camosine (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-camosine 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-kappa B 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-kappa B p65 on Ser276 and Ser536, and then, we exogenously blocked the NF-kappa B phosphorylation using Bay 11-7082. Based on our findings, L-camosine induces cell cycle arrest and apoptosis in human colorectal cancer cells by suppressing of NF- kappa B/STAT1 signaling.

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