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 language | English (US) |
|---|---|
| Pages (from-to) | 215-229 |
| Number of pages | 15 |
| Journal | Journal of Neuro-Oncology |
| Volume | 46 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2000 |
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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 journal › Article
}
TY - JOUR
T1 - Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture
AU - Casper, Diana
AU - Lekhraj, Rukmani
AU - Yaparpalvi, Umarani S.
AU - Pidel, Ann
AU - Jaggernauth, Wainwright A.
AU - Werner, Peter
AU - Tribius, Silke
AU - Del Rowe, John
AU - LaSala, Patrick A.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Acetaminophen
KW - Acetylsalicylate
KW - Glioma
KW - Ibuprofen
KW - NSAIDs
KW - Radiation
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=0034088903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034088903&partnerID=8YFLogxK
U2 - 10.1023/A:1006492423666
DO - 10.1023/A:1006492423666
M3 - Article
C2 - 10902853
AN - SCOPUS:0034088903
VL - 46
SP - 215
EP - 229
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 3
ER -