Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line

L. N. Nguyen, A. Munshi, M. L. Hobbs, M. D. Story, Jr Meyn R.D.

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose: To restore radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant murine lymphoma cell line (LY-ar) by pretreatment with paclitaxel (Taxol). Because this cell line also has high intracellular levels of glutathione (GSH), reportedly due to the bcl-2 expression and involved in the cell's antioxidant functions, paclitaxel treatment was correlated with GSH levels. Methods and Materials: LY-ar cells were pretreated with paclitaxel and then irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h later. Dose response and time course experiments were performed. Intracellular GSH levels were measured after treatment. Cell survival analysis was performed for various paclitaxel concentrations ± 5 Gy. Results: LY-ar cells pretreated with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel for 20 h underwent apoptosis at 2%, 15%, 25%, and 22%, respectively. With the addition of 5-Gy irradiation, LY-ar cell apoptosis increased to 4%, 30%, 49%, and 57%. Maximal apoptosis was detected with a paclitaxel pretreatment time of 20 h. Intracellular GSH levels were reduced by nearly 50% with paclitaxel pretreatment. Surviving fractions (SFs) with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05, respectively. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were 0.009, 0.003, 3 × 10-5, and 1 × 10-5, respectively. Conclusion: Radiation-induced apoptosis in LY-ar cells was restored by pretreatment with paclitaxel. This correlated with lowered levels of intracellular GSH. Cell survival analysis indicated that the combination of Taxol and radiation on cell killing was greater than additive.

Original languageEnglish (US)
Pages (from-to)1127-1132
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume49
Issue number4
DOIs
StatePublished - Mar 15 2001

Keywords

  • Apoptosis
  • Glutathione
  • Lymphoma
  • Paclitaxel
  • Radiation

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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