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Medicines 2018, 5(2), 58; https://doi.org/10.3390/medicines5020058

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

Division of Neurological Surgery, University of Missouri-Columbia School of Medicine, One Hospital Drive, MC 321, Columbia, MO 65212, USA
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Received: 23 May 2018 / Revised: 11 June 2018 / Accepted: 19 June 2018 / Published: 20 June 2018
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Abstract

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—Vitamin D3, Melatonin, and alpha-lipoic acid (LA)—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×1) activity assessed the anti-oxidant effect of TMZ +/− 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×1 effects. Conclusions: Anti-oxidants may have synergistic effects with TMZ. LA offers the most promise, followed by melatonin. View Full-Text
Keywords: glioblastoma; antioxidant therapy; vitamin D3; melatonin; lipoic acid; Temozolomide; MTT; oxidative stress; neural stem cells glioblastoma; antioxidant therapy; vitamin D3; melatonin; lipoic acid; Temozolomide; MTT; oxidative stress; neural stem cells
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McConnell, D.D.; McGreevy, J.W.; Williams, M.N.; Litofsky, N.S. Do Anti-Oxidants Vitamin D3, Melatonin, and Alpha-Lipoic Acid Have Synergistic Effects with Temozolomide on Cultured Glioblastoma Cells? Medicines 2018, 5, 58.

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