In vitro cytostatic activity and DNA-interaction of the new liver organotropic complex chloro-bis-cholylglycinate-platinum (II)

Anticancer Res. 1998 May-Jun;18(3A):1641-7.

Abstract

Background: The liver organotropic properties of the new bioinorganic complex of platinum (II) and glycocholic acid, Bamet-H2 have been reported previously. The aim of this work was to investigate the in vitro cytostatic activity of this compound.

Materials and methods: The inhibition of cell growth and DNA synthesis by mouse leukemia L-1210 (mL), mouse hepatoma Hepa 1-6 (mH), rat hepatoma McA-RH7777 (rH) and human colon adenocarcinoma LS-174T (hCC) cells were measured. The effects on the electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature and ethidium bromide (EthBr) binding to DNA were studied.

Results: A significant antiproliferative effect for Bamet-H2 was found (mH approximately hCC > mL approximately rH). DNA synthesis was also markedly inhibited (mH approximately hCC approximately mL approximately rH). Bamet-H2-induced a change in the electrophoretic mobility of pUC18 and the increase in DNA denaturation temperature suggested the existence of DNA-Bamet-H2 interactions. Scatchard plots obtained from EthBr displacement assays revealed that Bamet-H2 induces a reduction in both the number of DNA sites available and their ability to bind EthBr.

Conclusion: Bamet H2 is able to interact with DNA, inhibit DNA synthesis, and hence reduce cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Animals
  • Antineoplastic Agents / toxicity*
  • Cell Division / drug effects
  • Cell Line
  • Colonic Neoplasms / pathology*
  • DNA Replication / drug effects
  • DNA, Neoplasm / biosynthesis*
  • Ethidium / pharmacology
  • Humans
  • Kinetics
  • Leukemia L1210 / pathology
  • Liver Neoplasms, Experimental / pathology*
  • Mice
  • Nucleic Acid Denaturation
  • Organometallic Compounds / toxicity*
  • Rats
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Organometallic Compounds
  • bamet H2
  • Ethidium