Relation between intracellular accumulation and cytotoxic activity of cis-[((1R, 2R)-1, 2-cyclohexanediamine-N, N')bis(myristato)]platinum(II) suspended in Lipiodol

Biol Pharm Bull. 2003 May;26(5):683-6. doi: 10.1248/bpb.26.683.

Abstract

SM-11355, cis-[((1R, 2R)-1, 2-cyclohexanediamine-N, N')bis(myristato)]platinum(II), suspended in Lipiodol (SM-11355/Lipiodol) showed cytotoxic activity in hepatic tumor models in vivo and tumor cell lines in vitro. SM-11355/Lipiodol demonstrated selective retention in tumor tissue in vivo and high accumulation in tumor cells in vitro. This study was aimed to clarify the relation between the cytotoxicity of SM-11355/Lipiodol and intracellular platinum content. The cytotoxic activities were estimated by using WST-1 reagent. Intracellular platinum content and platinum-DNA adduct were estimated following exposure with SM-11355/Lipiodol when methionine was added. Methionine clearly inhibited the cytotoxic activities of SM-11355/Lipiodol. Moreover, intracellular platinum content and platinum-DNA adduct following exposure of SM-11355/Lipiodol decreased with increases in methionine concentration. The characteristic release of SM-11355/Lipiodol was not affected by addition of methionine. The present results suggested that one of platinum compounds exposed to cells following SM-11355/Lipiodol treatment is very similar in cytotoxic mechanism to cisplatin.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • DNA Adducts / biosynthesis
  • DNA Adducts / chemistry
  • DNA Adducts / metabolism
  • Drug Carriers
  • Drug Interactions
  • Iodized Oil*
  • Methionine / pharmacology
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Rats

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Drug Carriers
  • Organoplatinum Compounds
  • miriplatin
  • Iodized Oil
  • Methionine