STUDIES ON ENHANCEMENT OF ANTI-TUMOR EFFECT .1. COMBINATION ANTI-TUMOR EFFECT WITH CENTRAL NERVOUS-SYSTEM DEPRESSANTS ON RAT ASCITES HEPATOMAS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 71  (1) , 45-51
Abstract
Combined effects of 21 CNS depressants with several antitumor agents were studied in the in vitro and in vivo experimental systems, using rat ascites hepatoma cell lines, AH13 and AH44, sensitive and insensitive to alkylating agents, respectively. Reserpine remarkably enhanced the cytotoxic effect of 1-(.gamma.-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) on AH13 and AH44 cells. In the in vivo combined experiments, reserpine synergistically enhanced the life-prolonging effect of CAP-2 on AH13-bearing rats. Although CAP-2 was not potent on the prolongation of life span of AH44-bearing rats and reserpine was ineffective at the doses examined, the life span of tumor-bearing rats receiving the combined administration was apparently prolonged compared with control groups. There was a parallelism between in vitro and in vivo experiments. The antitumor-enhancing effect of reserpine might be due to the direct action on the tumor cells. A possible mechanism that reserpine inhibited the DNA damage-repairing activity of the cells was contradictory. Other mechanisms are also discussed.