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Background: Cancer patients often take over-the-counter anti-oxidants as primary treatment or in combination with chemotherapy. Data about such use in glioblastoma is limited. Methods: Cultured U87-MG cells, a primary glioblastoma cell line (MU1454), U87-MG derived stem-like cells (scU87), and MU1454 derived stem-like cell lines (scMU1454) were pre-treated with one of three anti-oxidants&amp;mdash;Vitamin D₃, Melatonin, and alpha-lipoic acid (LA)&amp;mdash;for 72 h, followed by a 72 h treatment with temozolomide (TMZ). MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assessed cell proliferation. DCFDA Cellular ROS Detection Assay and Glutathione peroxidase (GP&amp;times;1) activity assessed the anti-oxidant effect of TMZ +/&amp;minus; an anti-oxidant drug. Results : Vitamin D₃ did not affect MU1454, but had slight TMZ synergism for U87-MG. Melatonin 1 mM decreased U87-MG and MU1454 cell proliferation. As pretreatment to TMZ, melatonin 1 mM and 50 nM significantly reduced proliferation. LA 1 mM had a significant effect alone or with TMZ on U87-MG and MU1454. LA 250 uM also reduced proliferation by almost 50%. Melatonin and LA significantly enhanced the responsiveness of scMU1454 to TMZ, while Melatonin 50 nM exerted similar effects on scU87. The anti-oxidants were associated with generally decreased reactive oxygen species and limited GP&amp;times;1 effects. Conclusions: Anti-oxidants may have synergistic effects with TMZ. LA offers the most promise, followed by melatonin.

Do Anti-Oxidants Vitamin D3, Melatonin, and Alpha-Lipoic Acid Have Synergistic Effects with Temozolomide on Cultured Glioblastoma Cells?