Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells

Sarah A. Holstein, Huaxiang Tong, Raymond J. Hohl

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalLeukemia Research
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Farnesyl pyrophosphate
  • Geranylgeranyl pyrophosphate
  • Isoprenoid
  • Lovastatin
  • Myeloma
  • Thalidomide
  • Zoledronic acid

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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