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Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture
D Casper1, R Lekhraj, U S Yaparpalvi
1Department of Neurological Surgey, Montefiore Medical Center, Bronx, NY 10467, USA.
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.
Insights
Common pain relievers like acetaminophen show promise against glioblastoma multiforme (GBM). Acetaminophen induced apoptosis in glioma cells and sensitized them to radiation, suggesting therapeutic potential for this lethal brain cancer.
Area of Science:
- Neuro-oncology
- Pharmacology
- Cell Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive and lethal primary brain tumor.
- Current treatments for GBM have limited efficacy, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of common analgesics, specifically acetaminophen, on malignant glioma cell lines.
- To elucidate the mechanism of action of acetaminophen in glioma cells and assess its differential toxicity compared to normal brain cells.
- To evaluate the potential of acetaminophen in combination with ionizing radiation for GBM treatment.
Main Methods:
- Culturing of rodent and human malignant glioma cell lines and normal brain cells.
- Treatment with acetylsalicylate, acetaminophen, and ibuprofen to assess cytotoxicity and effects on cell proliferation, DNA synthesis, and mitotic index.
- Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect apoptosis.
- Assessment of glioma cell sensitivity to acetaminophen and ionizing radiation.
Main Results:
- Acetaminophen, acetylsalicylate, and ibuprofen reduced glioma cell numbers in vitro.
- Acetaminophen induced apoptosis in glioma cells, characterized by transient mitosis followed by cell death and DNA fragmentation.
- Glioma cells exhibited several-fold greater sensitivity to acetaminophen than normal brain cells.
- Subtoxic doses of acetaminophen enhanced the sensitivity of human glioma cells to ionizing radiation.
Conclusions:
- Acetaminophen demonstrates significant anti-glioma activity through apoptotic cell death.
- Acetaminophen exhibits a favorable therapeutic window, being more toxic to glioma cells than normal brain cells.
- Acetaminophen may serve as a valuable adjuvant therapy, potentially enhancing the efficacy of radiation treatment for glioblastoma.