Inhibition of methionine uptake by cis-diamminedichloroplatinum (II) in experimental brain tumors

Int J Cancer. 1996 Sep 4;67(5):681-3. doi: 10.1002/(SICI)1097-0215(19960904)67:5<681::AID-IJC15>3.0.CO;2-8.


cis-diamminedichloroplatinum (II) (CDDP) has been used both alone and in combination with other chemotherapeutics for cancer chemotherapy. Although CDDP acts primarily on DNA, it can also act at the tumor-cell membrane to inhibit methionine transport. The latter mechanism of CDDP is reported to have an important role as a chemical modulator in enhancing chemotherapeutic effects of 5-fluorouracil in tumor cells. We report here the effects of CDDP on methionine uptake in an in vivo brain-tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-week-old male Sprague-Dawley rats. Ten days after the inoculation, autoradiographic images were obtained using (14C-methyl)-L-methionine. The tracer uptake, represented as differential absorption ratio (DAR) and an acid-insoluble fraction (AIF), was measured in both brain tumors and normal brain with or without an intravenous injection of CDDP. The tumor/non-tumor DAR and AIF decreased significantly (P < 0.01, as determined by the Mann-Whitney U-test) after CDDP treatment, whereas the non-tumor DAR and AIF remained almost unchanged. These findings indicate that CDDP inhibits methionine uptake selectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Autoradiography
  • Biological Transport / drug effects
  • Brain Neoplasms / metabolism*
  • Cisplatin / pharmacology*
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Methionine / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Methionine
  • Cisplatin