Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture

Diana Casper, Rukmani Lekhraj, Umarani S. Yaparpalvi, Ann Pidel, Wainwright A. Jaggernauth, Peter Werner, Silke Tribius, John Del Rowe, Patrick A. LaSala

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture. However, their mechanisms of action may vary, as demonstrated by (1) differences in the morphological changes produced by these compounds; (2) varied responses to these drugs with respect to toxicity kinetics; and (3) respective rates of cell proliferation, DNA synthesis, and mitotic index. We studied the effects of acetaminophen on relative cell number further. Evidence is presented that acetaminophen induced cell death by an apoptotic mechanism after a brief burst of mitosis in which cell numbers increased transiently, followed by a reduction in cell number and an increase in DNA fragmentation, as evidenced by terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using cultures of adult human brain and embryonic rat brain, we demonstrated that glioma cells were several-fold more sensitive to acetaminophen than normal brain cells in culture. Finally, subtoxic doses of acetaminophen increased the sensitivity of the human glioma cells in culture to ionizing radiation. Taken together, these results suggest that acetaminophen may prove to be a useful therapeutic agent in the treatment of human brain tumors.

Original languageEnglish (US)
Pages (from-to)215-229
Number of pages15
JournalJournal of Neuro-Oncology
Volume46
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Radiation Tolerance
Acetaminophen
Glioma
Growth
Cell Count
Brain Neoplasms
Brain
Cell Culture Techniques
Mitotic Index
Ibuprofen
In Situ Nick-End Labeling
DNA Fragmentation
Glioblastoma
Biotin
Ionizing Radiation
Mitosis
Rodentia
Cell Death
Cell Proliferation
Cell Line

Keywords

  • Acetaminophen
  • Acetylsalicylate
  • Glioma
  • Ibuprofen
  • NSAIDs
  • Radiation
  • Toxicity

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture. / Casper, Diana; Lekhraj, Rukmani; Yaparpalvi, Umarani S.; Pidel, Ann; Jaggernauth, Wainwright A.; Werner, Peter; Tribius, Silke; Del Rowe, John; LaSala, Patrick A.

In: Journal of Neuro-Oncology, Vol. 46, No. 3, 2000, p. 215-229.

Research output: Contribution to journalArticle

Casper, D, Lekhraj, R, Yaparpalvi, US, Pidel, A, Jaggernauth, WA, Werner, P, Tribius, S, Del Rowe, J & LaSala, PA 2000, 'Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture', Journal of Neuro-Oncology, vol. 46, no. 3, pp. 215-229. https://doi.org/10.1023/A:1006492423666
Casper, Diana ; Lekhraj, Rukmani ; Yaparpalvi, Umarani S. ; Pidel, Ann ; Jaggernauth, Wainwright A. ; Werner, Peter ; Tribius, Silke ; Del Rowe, John ; LaSala, Patrick A. / Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture. In: Journal of Neuro-Oncology. 2000 ; Vol. 46, No. 3. pp. 215-229.
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