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Journal of the National Cancer Institute

Potentiation of anticancer agents by new synthetic isoprenoids. II. Inhibition of the growth of transplantable murine tumors.


PMID 6207332

Abstract

The antitumor effects of combinations of synthetic isoprenoids-decaprenylamine.HCl, N-(p-methylbenzyl)decaprenylamine.HCl [N-(PMB)-decaprenylamine.HCl], and decaprenoic acid-with anticancer agents were studied in male ICR mice with ascites sarcoma 180 (S180) and in male BALB/c mice with fibrosarcoma Meth A. Decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl, and decaprenoic acid were tested in combination with bleomycin A2 (BLM) on S180. Decaprenoic acid was also examined in combination with BLM or 5-fluorouracil (FUra) for effects on fibrosarcoma Meth A. The dosages of synthetic isoprenoids used in the combination therapy were much below the median lethal dose. In the low-dosage schedule, decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl or decaprenoic acid considerably enhanced the antitumor effect of BLM on S180; e.g., the T/C value (mean survival time of treated mice/mean survival time of controls) for decaprenylamineHCl plus BLM, N-(PMB)-decaprenylamine.HCl plus BLM, or decaprenoic acid plus BLM was 294, 357, and 279% respectively, and the combinations increased life-span 2.4-fold, 2.3-fold, or 1.8-fold, respectively, as compared to the effects of BLM alone. The combination of BLM or FUra with decaprenoic acid, when administered by iv injection to mice with fibrosarcoma Meth A (solid tumor system), did not produce synergism. However, a preventive effect of decaprenoic acid monotherapy was observed: Decaprenoic acid at 3 mg/kg resulted in 38.9% suppression of tumor growth 21 days after inoculation.

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