Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture

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