Cisplatin increases sensitivity of human leukemic blasts to triazene compounds

D. Piccioni, S. D'Atri, G. Papa, T. Caravita, A. Franchi, E. Bonmassar, G. Graziani

Research output: Contribution to journalArticlepeer-review

Abstract

High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O6-alkylguanine alkylating agents, including triazene compounds. A pilot clinical study indicates that dacarbazine can induce a marked decrease of leukemic blasts in patients affected by acute myelogenous leukemia (AML) with low pretreatment levels of OGAT activity. In this study we show a synergistic antitumor effect between cisplatin (CDDP) and temozolomide (an in vitro active analog of dacarbazine), following combined in vitro treatment of leukemic blasts. Synergistic effect appears to be CDDP-dose dependent. In vivo treatment of leukemic patients with CDDP was followed by a reduction of OGAT activity in 2 out 3 cases. These data point out that CDDP could be a good candidate for depleting OGAT protein of leukemic cells, thus reversing tumor cell resistance to dacarbazine.

Original languageEnglish
Pages (from-to)224-229
Number of pages6
JournalJournal of Chemotherapy
Volume7
Issue number3
Publication statusPublished - 1995

Keywords

  • Cisplatin
  • Dacarbazine
  • Leukemia
  • O-alkylguanine-DNA-alkyltransferase
  • Temozolomide

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)

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