Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine

David B. Jendiroba, Jim Klostergaard, Afsaneh Keyhani, Lance Pagliaro, Emil J. Freireich

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.

Original languageEnglish (US)
Pages (from-to)301-310
Number of pages10
JournalLeukemia Research
Volume26
Issue number3
DOIs
StatePublished - Jan 15 2002

Keywords

  • Cytotoxicity
  • Dimethylsphingosine
  • Leukemia patients
  • Sphingolipids

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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