In vitro interactions of a new derivative of spicamycin, KRN5500, and other anticancer drugs using a three-dimensional model

Cancer Chemother Pharmacol. 1999;43(5):353-63. doi: 10.1007/s002800050907.

Abstract

Purpose: KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against human cancer cell lines. Because of its unique structure, this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore, KRN5500 is expected to be a suitable candidate for combination chemotherapy.

Methods: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model.

Results: Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 microg/ml and 0.025 to 0.25 microg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic interaction was also found.

Conclusion: These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Division / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Etoposide / administration & dosage
  • Etoposide / pharmacology
  • Humans
  • Lung Neoplasms / pathology*
  • Models, Biological
  • Models, Statistical
  • Purine Nucleosides / administration & dosage
  • Purine Nucleosides / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Purine Nucleosides
  • Etoposide
  • KRN 5500
  • Carboplatin
  • Cisplatin