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Antitumor Molecular Mechanism of Chlorogenic Acid on Inducting Genes GSK-3β and APC and Inhibiting Gene β-Catenin

DOI: 10.1155/2013/951319

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Abstract:

Objective. Inhibiting gene β-catenin and inducting genes GSK-3β and APC, promoting the tumor cell apoptosis in Wnt pathway, by chlorogenic acid were discussed (CGA). Method. The different genes were scanned by the 4*44K mouse microarray chips. The effect of the three genes was confirmed by RT-PCR technique with CGA dosage of 5, 10, and 20?mg/kg. Result. The expression of GSK-3β and APC was upregulated in group of 20?mg/kg dosage ( ) and the expression of β-catenin was downregulated in the same dosage ( ). Conclusion. The results infer that the multimeric protein complex of β-catenin could be increased by CGA upregulated genes GSK-3β and APC, which could inhibit the free β-catenin into the nucleus to connect with TCF. So the transcriptional expression of the target genes will be cut to abnormal cell proliferation. It is probably one of the ways that can stop the tumor increase by CGA. 1. Introduction Chlorogenic acid is the ester of caffeic acid and quinic acid in shikimate pathway, which is commonly found in some plants, such as honeysuckle, Cortex Eucommiae, Semen Coffea Arabica, and green tea. Chlorogenic acid has antibacterial, antiviral, clear free radicals, and antitumor effects [1]. In recent years, the effective anticancer activity and low toxicity of chlorogenic acid were constantly confirmed and draw the attention of the people [2–4]. Kurata et al. [5] showed that the inhibition of tumor cell proliferation effect of chlorogenic acid was enhanced with increasing dose; they speculated that this inhibition of tumor cell proliferation may be obtained by enhancing the activity of the DNA ladder and caspase-3 as well as increasing the expression of c-Jun. Gmnado and Feng et al. showed that the in vitro experiments show that the anticancer mechanism of CGA contains inhibition of cell growth, regulation of cell cycle, and induction of apoptosis pathways, such as (1) to reduce ROS expression to reduce cell growth/reproduction signal transduction pathway of NF-κB, AP-l, and MAPKs to reduce cancer cell viability, (2) to improve the activity of the NAD (P)H and GST, (3) to inhibit the expression of tetradecanoyl method wave alcohol acetate (TPA), in order to reduce the c-Jun NH2-terminal kinase, p38 kinase, and MAPK kinase-4 to prevent cancer transformation, and (4) to stimulate the expression of NF-E2-related factor and the activity of GST regulated by Nrf2 downstream cascade links antioxidant response element (ARE) to inhibit the growth of cancer cells [6, 7]. Chlorogenic acid is considered to be an effective cancer chemical repellant because of its

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