The Inhibitory Effect of the Combination of Antineoplaston A‐10 Injection with a Small Dose of cis‐Diamminedichloroplatinum on Cell and Tumor Growth of Human Hepatocellular Carcinoma

Abstract

The inhibitory effects of a combination of Antineoplaston A‐10 Injection with a small dose of m‐diamminedichloroplatinum (CDDP) on cell and tumor growth was tested in in vitro and in vivo settings. A human hepatocellular carcinoma cell line (KIM‐1) was used for the cell growth and transplanted tumor growth studies. In the cell growth study, one‐hour exposure of KIM‐1 cells to CDDP in the medium at concentrations of 0.5, 1.0, and 2.0 μg/ml inhibited cell growth dose‐dependently. Continuous exposure of cultured cells to Antineoplaston A‐10 Injection at concentrations of 4, 6, and 8 mg/ml also inhibited tumor growth dose‐dependently. The combination of 0.5 μg/ml CDDP and 6 mg/ml A‐10 Injection inhibited cell growth more than did each agent individually. Electron microscopic study showed well‐maintained organelle structures in Antineoplaston A‐10 Injection‐treated cells compared to CDDP‐treated cells. α‐Fetoprotein (AFP) production by 104 cells in 48 h increased in the A‐10 Injection‐treated and A‐10 Injection + CDDP‐treated groups as the concentration of these agents increased. In the tumor growth study, daily administration of Antineoplaston A‐10 Injection 75 mg with once a week administration of 20 μg of CDDP for 5 weeks inhibited transplanted tumor growth in athymic mice after 33 days of treatment, while administration of 75 mg of A‐10 Injection or 20 or 60 μg of CDDP alone showed no significant inhibition of tumor growth.

Infrared Matrix Isolation and Theoretical Studies on Glutarimide

“…Several glutarimide derivatives have been reported to possess significant anticancer activity. For example, PCNU [λ-(chloroethyl)-3-(2,6-piperidinedione)-1-nitrosourea] can easily cross the blood−brain barrier, and it shows activity against brain tumors; aminoglutethimide is a strong inhibitor of steroid biogenesis and is used in the treatment of metastatic breast cancer; and antineoplaston A10 ( N -phenylacetyl-α-aminoglutarimide), which has recently been introduced into experimental chemotherapy, has a remarkable anticancer activity, particularly against brain tumors, and it shows very low toxicity. , In vitro studies employing the thermal denaturation of DNA as well as fluorescence spectroscopy have revealed that antineoplaston A10 may bind weakly and noncovalently with DNA . Eriguchi et al .…”

Long-Term Survival Following Treatment with Antineoplastons for Colon Cancer with Unresectable Multiple Liver Metastases: Report of a Case

“…16 Antineoplaston AS2-1 has shown a cell differentiation effect in many malignant cells such as human erythroleukemic cells (K562) 17 and human hepatocellular carcinoma cells (KIM-1). 18 These findings suggest the diverse effects of antineoplaston AS2-1 on the genes controlling cell differentiation.…”

The Effect of Antineoplaston, a New Antitumor Agent on Malignant Brain Tumors.

“…They found AS2-1 to induce cell differentiation, as shown by hemoglobin production in erythroleukemia cells. Tsuda et al (1992) demonstrated in an electron microscopic study that A-10 injection in combination with small doses of CDDP induces morphological differentiation in human hepatocellular carcinoma. Liau et al (1989) suggest that the hypomethylation of nucleic acids by AS2-1 may be essential for inducing cell differentiation.…”