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

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.

• Authors: T Yamaguchi, K Ikezaki, T Kishiye, Y Tahara, H Koyama, T Takahasi, H Fukawa, S Komiyama, S Akiyama, M Kuwano
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 73 Issue 4 Pg. 903-7 (Oct 1984) ISSN: 0027-8874 [Print] United States
• PMID: 6207332 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• N-(4-methylbenzyl)decaprenylamine
• Terpenes
• Bleomycin
• decaprenylamine
• Doxorubicin
• decaprenoic acid
• Fluorouracil

Topics

• Animals
• Antineoplastic Agents (toxicity)
• Bleomycin (toxicity)
• Doxorubicin (toxicity)
• Drug Evaluation, Preclinical
• Drug Synergism
• Fibrosarcoma (pathology)
• Fluorouracil (toxicity)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Sarcoma 180 (pathology)
• Structure-Activity Relationship
• Terpenes (toxicity)