Demethylation effect of the antineoplaston AS2-1 on genes in colon cancer cells

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Abstract

Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplastons have been shown to control neoplastic growth. In the present study, we investigated demethylation effect of the antineoplaston AS2-1 (a mixture of phenylacetylglutamine and phenylacetate in the ratio of 1:4) on various genes in colon cancer cells. An HpaII-MspI methylation microarray was used to investigate the methylation status of 51 genes at the promoter region in HCT116 and KM12SM human colon cancer cells before and after treatment of AS2-1. The expression of protein and mRNA of the demethylated genes by AS2-1 in HCT116 cells was evaluated. In 19 of the 34 methylated genes in HCT116 and in 7 of the 8 methylated genes in KM12SM, the methylation status was downregulated after treatment with 2 mg/ml of AS2-1 for 24 h. AS2-1 dramatically downregulated the methylation status of p15 and ESR1 in HCT116 cells and of MTHFR and MUC2 in KM12SM cells. Both mRNA and protein expression of p15 increased in a dose- and time-dependent manner after treatment with AS2-1. The antineoplaston AS2-1 may normalize the hypermethylation status at the promoter region in various genes including tumor suppressor genes, resulting in activation of the transcription and translation in colon cancer.

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Ushijima, M., Ogata, Y., Tsuda, H., Akagi, Y., Matono, K., & Shirouzu, K. (2014). Demethylation effect of the antineoplaston AS2-1 on genes in colon cancer cells. Oncology Reports, 31(1), 19–26. https://doi.org/10.3892/or.2013.2839

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