In vitro assessment of nucleoside analogs in multiple myeloma

Nancy L. Krett, Mary Ayres, Chadi Nabhan, Chunguang Ma, Billie Nowak, Steffan Nawrocki, Steven T. Rosen, Varsha Gandhi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: To identify nucleoside analogs that may be effective for multiple myeloma (MM), we tested fludarabine, clofarabine, arabinosylguanine, cytarabine, troxacitabine, and gemcitabine in MM cell lines. Methods: We employed biologic and biochemical assays in MM cell lines to evaluate the clinical potential of these nucleoside analogs. Results: Among these purine and pyrimidine nucleoside analogs, fludarabine, clofarabine and gemcitabine were the most potent. MM cell lines, resistant to commonly used chemotherapeutic agents for this disease, were more sensitive to gemcitabine with an IC50 in the nanomolar range. The greater cytotoxicity of gemcitabine in MM cells was consistent with greater accumulation of gemcitabine triphosphate, the major cytotoxic metabolite of this drug. MM.1S cells accumulated > 100 μM gemcitabine triphosphate but accumulated < 20 μM of the other analogs as the respective triphosphates. In addition incubation with gemcitabine resulted in inhibition of DNA synthesis. Incubation with 25, 50 or 100 n M gemcitabine resulted in a dose- and time-dependent increase in the cell population with a subG1 DNA content indicative of apoptosis. Conclusions: These results suggest that gemcitabine is a potent nucleoside analog in MM cell lines including cell types resistant to other chemotherapeutic agents. The greater activity of gemcitabine compared to other analogs seems to be due to favorable metabolism of this agent.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume54
Issue number2
StatePublished - Aug 2004
Externally publishedYes

Fingerprint

gemcitabine
Multiple Myeloma
Nucleosides
Cells
Cell Line
Pyrimidine Nucleosides
Purine Nucleosides
In Vitro Techniques
DNA
Cytarabine
Cytotoxicity
Metabolites
Metabolism
Biological Assay
Inhibitory Concentration 50
Assays

Keywords

  • Gemcitabine
  • Multiple myeloma
  • Nucleoside analogs

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Krett, N. L., Ayres, M., Nabhan, C., Ma, C., Nowak, B., Nawrocki, S., ... Gandhi, V. (2004). In vitro assessment of nucleoside analogs in multiple myeloma. Cancer Chemotherapy and Pharmacology, 54(2), 113-121.

In vitro assessment of nucleoside analogs in multiple myeloma. / Krett, Nancy L.; Ayres, Mary; Nabhan, Chadi; Ma, Chunguang; Nowak, Billie; Nawrocki, Steffan; Rosen, Steven T.; Gandhi, Varsha.

In: Cancer Chemotherapy and Pharmacology, Vol. 54, No. 2, 08.2004, p. 113-121.

Research output: Contribution to journalArticle

Krett, NL, Ayres, M, Nabhan, C, Ma, C, Nowak, B, Nawrocki, S, Rosen, ST & Gandhi, V 2004, 'In vitro assessment of nucleoside analogs in multiple myeloma', Cancer Chemotherapy and Pharmacology, vol. 54, no. 2, pp. 113-121.
Krett NL, Ayres M, Nabhan C, Ma C, Nowak B, Nawrocki S et al. In vitro assessment of nucleoside analogs in multiple myeloma. Cancer Chemotherapy and Pharmacology. 2004 Aug;54(2):113-121.
Krett, Nancy L. ; Ayres, Mary ; Nabhan, Chadi ; Ma, Chunguang ; Nowak, Billie ; Nawrocki, Steffan ; Rosen, Steven T. ; Gandhi, Varsha. / In vitro assessment of nucleoside analogs in multiple myeloma. In: Cancer Chemotherapy and Pharmacology. 2004 ; Vol. 54, No. 2. pp. 113-121.
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