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

Published on Friday, 22 June 2018


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 GPx1 effects.

Conclusions: Anti-oxidants may have synergistic effects with TMZ. LA offers the most promise, followed by melatonin.


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See also:

- About Melatonin;

- The Di Bella Method (A Fixed Part - Melatonin tablets);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- Vitamin D (analogues and/or derivatives) and cancer;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives);

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E);

- The Di Bella Method (A Fixed Part - Cyclophosphamide and/or Hydroxyurea tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Vitamin C/Ascorbic Acid, 2–4 grams per day, orally);

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Neuroblastoma: Complete objective response to biological treatment;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.