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Antitumor activity of spergualin, a novel antitumor antibiotic.

Abstract
Spergualin (SGL), a novel antitumor antibiotic, exhibited strong antitumor activity against transplantable leukemias in mice: L1210, L1210(IMC), P388, P815, C1498, EL-4 and RL male 1. It also exhibited antitumor activity against M5076 fibrosarcoma, AH66 and AH66F rat hepatomas, but not against Meth-A fibrosarcoma, B16 melanoma, Lewis lung carcinoma (LL) and C26 colon adenocarcinoma. The antitumor activity of SGL was administration-schedule dependent. The strongest activity against L1210 was obtained by ip continuous infusion for 7 days or daily ip administration for 9 days. Single ip injection of SGL at 100 mg/kg to mice caused convulsion and death within 15 minutes after injection. Such acute toxicity was not observed by continuous infusion. SGL showed its strongest activity at subtoxic dose against sensitive tumors except for L1210(IMC). Mice implanted ip with L1210(IMC) were cured by treatment with SGL at 3.13 mg/kg/day for 9 days, but died from the tumor at 50 mg/kg/day X 9. The cured mice rejected a second inoculation of up to 10(6) tumor cells. The tumor cells isolated from mice after treatment with the high dose showed resistance to SGL in vivo. Mice implanted sc with L1210(IMC) were also cured by 9 daily ip administrations of SGL at 12.5 mg/kg/day, but solid tumor was observed at the implantation site until 3 days after the final injection of SGL in some cured mice. These results suggest that the therapeutic effect of SGL has a relatively high specificity for leukemias and that the immunological effect is involved in the antitumor activity.
AuthorsK Nishikawa, C Shibasaki, K Takahashi, T Nakamura, T Takeuchi, H Umezawa
JournalThe Journal of antibiotics (J Antibiot (Tokyo)) Vol. 39 Issue 10 Pg. 1461-6 (Oct 1986) ISSN: 0021-8820 [Print] England
PMID3781914 (Publication Type: Journal Article)
Chemical References
  • Antibiotics, Antineoplastic
  • Guanidines
  • spergualin
Topics
  • Animals
  • Antibiotics, Antineoplastic (administration & dosage, pharmacology, therapeutic use)
  • Guanidines (administration & dosage, pharmacology, therapeutic use)
  • Leukemia L1210 (drug therapy)
  • Leukemia P388 (drug therapy)
  • Leukemia, Experimental (drug therapy)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred ICR
  • Neoplasm Transplantation
  • Neoplasms, Experimental (drug therapy)
  • Rats

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