Doxorubicin and vincristine with methionine depletion contributed to survival in the Yoshida sarcoma bearing rats

Anticancer Res. Jan-Feb 1998;18(1A):25-31.


Several anti-cancer agents show increased toxicity if administered with methionine-depleting total parenteral nutrition (Met-deplete TPN). Changes in the cell cycle due to Met-deplete TPN were investigated, and then the enhancement of the anti-tumor effects of serial combinations of doxorubicin (ADM), a drug acting on late S-G2 phase and vincristine (VCR), an antimitotic drug, under Met-deplete TPN was also examined in the tumor-bearing rats. According to the fraction of labeled mitosis, within 3 to 4 days after the introduction of Met-deplete TPN in the ascites type Yoshida sarcoma (YS) -bearing rats, the cell cycle of the tumor cells showed marked delay and the fraction of labeled mitosis decreased to less than 70%. However, this delay was recovered immediately after methionine infusion, with on increase in the labeled mitotic cell population. In the experiment using solid type YS-bearing rats, ADM was administered intraperitoneally under Met-deplete TPN for 8 days, followed by intraperitoneal VCR administration with methionine-containing TPN for 3 days, and then fed on solid food and water ad libitum until death. This serial combination of Met-deplete TPN with ADM and VCR resulted in marked suppression of the tumor and prolonged survival in comparison to the control groups with a significant difference (p < 0.001) (generalized Wilcoxon test).

MeSH terms

  • Animals
  • Cell Cycle
  • Doxorubicin / administration & dosage*
  • Male
  • Methionine / deficiency*
  • Mitosis
  • Parenteral Nutrition, Total
  • Rats
  • Sarcoma, Yoshida / drug therapy*
  • Sarcoma, Yoshida / pathology
  • Survival Analysis
  • Vincristine / administration & dosage*


  • Vincristine
  • Doxorubicin
  • Methionine