Abstract Number: 2976
Antitumor effect of biochemical defense modifier Antineoplaston AS2-1 against colon cacer through G1 and G2 cell arrest
Matono Keiko. Kurume University, Kurume City, Japan.
Introduction: Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine, were first described by Burzynski in 1976.
The small peptides reportedly control neoplastic growth and have minimum adverse effects. However, the molecular mechanisms of the antitumor effects are not well known.
In the present study, we have investigated antitumor mechanisms of Antineoplaston AS2-1 against colon cancer cells with regard to cell cycle.
Methods: We tested Antineoplaston AS2-1 on in vitro and in vivo cell growth activity in human colon cancer cells (KM12SM, SW620, SW1417, Colo205, HCT116). And we analyzed cell cycle by FACS and expression of cell cycle regulators by western blot.
Results: Antineoplaston AS2-1 inhibited proliferation of all human colon cancer cells in a dose and a time dependent manner in vitro.
Antineoplaston AS2-1 inhibited tumor growth of nude mice implanted by human colon cancer cells KM12SM and HCT116 in a dose and a time dependent manner in vivo.
We demonstrated G1 cell arrest in short time treatment with AS2-1. However, by treatment with high dosage (5mg/ml) of AS2-1 for long time(3 days) the cell cycle analysis showed increase of the G2 phase cells.
The protein levels of cyclin-dependent kinase (cdk)-2, cyclin E, cdk-4, cyclin D in the colon cancer cells significantly decreased and the level of p16 and p21 increased time and dose dependently with antineoplaston AS2-1 treatment.
And antineoplaston AS2-1 decreased the level of phosphorylated retinoblastoma protein. The protein levels of cyclin A, cdc2, cyclinB1 which can control G2 phase were decreased by high dose and long term treatment with AS2-1.
We confirmed that these results did not come from glutamine deficiency. We have further investigated influence on methylation status and induction of apoptosis by treatment with AS2-1.
Conclusion: Antineoplaston AS2-1 shows antitumor effects against colon cancer through both the G1 and G2 cell arrests and we have applied the antineoplaston AS2-1 as an adjuvant therapy after hepatic resection of colorectal metastases in combination with hepatic arterial infusion chemotherapy.
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