Anti-tumor effects of biochemical defense modifier antineoplaston again colorectal cancer

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(in vitro study)Antineoplaston AS2-1 inhibited colon cancer cell (KM12SM, SW620, SW1417, Colo206, HCTI16) proliferation in a dosage-and time-dependent manner through G1 cell arrest and induction of apoptosis. AS2-1 up-regulated the protein expression of cyclin D and cyclin E, and down-regulated the protein expression of p-16 and p21, resulting down-regulated the protein level of phosphorylated Rb in KM12SM and HCT116 cells. Five mg/ml of AS2-1 induced apoptosis in tumor cells through down-regulation of XIAP and up-regulation of caspase 3 and caspase 8. Methyl scan DNA chip study revealed that AS2-1 normalized or reduced the hyper methylation in various genes.(in vivo study)AS2-1 inhibited the growth and tumorigenecity of implanted colon tumors (KM121SM, HCT116) into the subcutis in nude mice. AS2-1 showed significant reduction in lung metastasis and prolongation of survival time using removal model of orthotopically implanted colon cancer in nude rats.(Clinical study)We have conducted a randomized control study after hepatectomy in colorectal metastasis to the liver. Hepatic arterial infusion chemotherapy using 5-FU with or without antineoplastons was performed in 64 patients between 1998 and 2004. There was no significant difference in disease-free survival rate between the two groups, however the survival rates in antineoplaston group was tended to be higher than that in the control group. Further follow-up should be necessary to conclude usefulness of antineoplastons.Antineoplastons would be effective in colorectal cancer in particular in adjuvant setting in combination with cytotoxic chemotherapeutic agents.