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

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.

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Effect Of alpha-Lipoic Acid On Lipid Peroxidation And Anti-Oxidant Enzyme Activities In Diabetic Rats

Clinical and Experimental Pharmacology and Physiology ◽

10.1046/j.1440-1681.2002.03642.x ◽

2002 ◽

Vol 29 (4) ◽

pp. 281-284 ◽

Cited By ~ 39

Author(s):

Yildiz Dincer ◽

Aysegul Telci ◽

Refik Kayali ◽

Ilker A Yilmaz ◽

Ufuk Cakatay ◽

...

Keyword(s):

Lipid Peroxidation ◽

Lipoic Acid ◽

Enzyme Activities ◽

Diabetic Rats ◽

Alpha Lipoic Acid ◽

Anti Oxidant

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Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway

International Journal of Endocrinology ◽

10.1155/2014/658589 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 10

Author(s):

Chuan Lv ◽

Can Wu ◽

Yue-hong Zhou ◽

Ying Shao ◽

Guan Wang ◽

...

Keyword(s):

Cell Cycle ◽

Extracellular Matrix ◽

Cell Proliferation ◽

Lipoic Acid ◽

High Glucose ◽

Mesangial Cell ◽

Mesangial Cells ◽

S Phase ◽

Alpha Lipoic Acid ◽

Mesangial Cell Proliferation

The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I (collagen-I) expression and its mechanisms were examined in cultured rat mesangial cells by methylthiazol tetrazolium (MTT) assay, flow cytometry, ELISA assay, and western blot, respectively. LA at a relatively low concentration (0.25 mmol/L) acted as a growth factor in rat mesangial cells, promoted entry of cell cycle into S phase, extracellular matrix formation, and phosphorylated AKT, mTOR, p70S6K, and 4E-BP1. These effects disappeared when AKT expression was downregulated with PI3K/AKT inhibitor LY294002. Conversely, LA at a higher concentration (1.0 mmol/L) inhibited high glucose-induced rat mesangial cell proliferation, entry of cell cycle into S phase, and extracellular matrix exertion, as well as phosphorylation of mTOR, p70S6K, and 4E-BP1 but enhanced the activity of AMPK. However, these effects disappeared when AMPK activity was inhibited with CaMKK inhibitor STO-609. These results suggest that LA dose-dependently regulates mesangial cell proliferation and matrix protein secretion by mTOR/p70S6K/4E-BP1 signaling pathway under high glucose conditions.

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The Effect of Alpha Lipoic Acid (ALA) on S. cerevisiae Cell Proliferation

American Journal of Medical and Biological Research ◽

10.12691/ajmbr-6-2-1 ◽

2018 ◽

Vol 6 (2) ◽

pp. 21-26

Author(s):

Henna Purewal

Keyword(s):

Cell Proliferation ◽

Lipoic Acid ◽

Alpha Lipoic Acid

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Effects of individual or combined use of alpha-lipoic acid and methylprednisolone on malondialdehyde, superoxide dismutase, and catalase levels in acute spinal cord injury in rats

Journal of Health Sciences ◽

10.17532/jhsci.2016.409 ◽

2016 ◽

Vol 6 (3) ◽

pp. 174-183

Author(s):

Alper Birgul ◽

Gokhan Canaz ◽

Murat Ugur ◽

Mehmet Tokmak ◽

Metin Kasap ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Superoxide Dismutase ◽

Lipoic Acid ◽

Synergistic Effects ◽

Alpha Lipoic Acid ◽

Sprague Dawley ◽

Combined Use ◽

Significant Difference ◽

Cord Injury

Introduction: Recent studies have demonstrated that alpha-lipoic acid (ALA) has a strong antioxidant property and it exerts neurotrophic effects on the peripheral nerves. In this study, we investigated potential effects of ALA on secondary injury mechanisms as well as on apoptosis.Methods: Forty Sprague-Dawley rats were equally divided into 5 groups, as follows: laminectomy (control), laminectomy + trauma (Trauma), laminectomy + posttraumatic methylprednisolone [MP] (Trauma + MP), laminectomy + posttraumatic ALA (Trauma + ALA), laminectomy + posttraumatic MP and ALA (Trauma + MP + ALA). Yasargil aneurysm clip method was used to induce the spinal cord injury. Twenty-four hours after the procedure the rats were sacrificed. Spinal cord samples were harvested to analyze malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels, as well as histopathological characteristics.Results: The Kruskal-Wallis test (95% confidence level, p < 0.05) showed a statistically significant difference between the groups in MDA (p = 0.006), CAT (p = 0.000), and SOD (p = 0.001) levels. Pairwise comparisons, with Bonferroni correction, of control and Trauma group with the other groups, revealed a significant difference in CAT and SOD levels. Overall, our results showed that ALA administration significantly decreased MDA levels in Trauma + ALA compared to the same effect of MP in Trauma + MP group. Furthermore, ALA administration increased SOD and CAT levels in Trauma + ALA group. The combined use of ALA and MP demonstrated synergistic effects and yielded even more significant results.Conclusions: A combined use of ALA and MP might provide a benefit in patients exposed to spinal cord injury. However, at present, further studies are required to confirm these results.

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Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652013005000023 ◽

2013 ◽

Vol 85 (2) ◽

pp. 745-752 ◽

Cited By ~ 15

Author(s):

Jyh-Gang Leu ◽

Chin-Yao Lin ◽

Jhin-Hao Jian ◽

Chin-Yu Shih ◽

Yao-Jen Liang

Keyword(s):

Advanced Glycation End Products ◽

Lipoic Acid ◽

High Glucose ◽

Alpha Lipoic Acid ◽

Human Embryonic Kidney ◽

Advanced Glycation ◽

Hek Cells ◽

Glycation End Products ◽

End Products ◽

Anti Oxidant

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

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Effect of Alpha-Lipoic Acid Supplementation on Endothelial Function and Cardiovascular Risk Factors in Overweight/Obese Youths: A Double-Blind, Placebo-Controlled Randomized Trial

Nutrients ◽

10.3390/nu11020375 ◽

2019 ◽

Vol 11 (2) ◽

pp. 375 ◽

Cited By ~ 11

Author(s):

Luciana Tromba ◽

Francesco Perla ◽

Giovanni Carbotta ◽

Claudio Chiesa ◽

Lucia Pacifico

Keyword(s):

Risk Factors ◽

Endothelial Function ◽

Lipoic Acid ◽

Brachial Artery ◽

Normal Weight ◽

Alpha Lipoic Acid ◽

Double Blind ◽

Blinded Manner ◽

Anti Oxidant ◽

Double Blinded

Endothelial dysfunction is recognized as an early sign of systemic atherosclerosis, and it represents a therapeutic target to prevent long-term cardiovascular (CV) consequences. Alpha-lipoic acid (ALA) is a commonly used dietary supplement exerting anti-oxidant and anti-inflammatory effects. We investigated whether a three-month treatment with ALA improves endothelial function, as assessed by flow-mediated dilation (FMD) of the brachial artery, and clinical and metabolic risk factors in overweight/obese youths. We enrolled 67 overweight/obese children, and 22 normal-weight metabolically healthy controls. Overweight/obese youths were randomly allocated in a double-blinded manner to receive ALA (n = 34) or placebo (n = 33). Of these, 64 (32 ALA, 32 placebo) completed the follow-up. At baseline, in ALA and placebo groups, FMD was similar, but lower as compared with that in controls (p = 0.045). At three months, within the ALA and placebo groups, FMD did not change significantly. However, the basal and peak diameter of brachial artery significantly increased after ALA treatment as compared to placebo (p = 0.036 and p = 0.01, respectively). There were no significant within- and between-group changes for anthropometric and metabolic variables. The results show that ALA supplementation improves vascular tone and may have a beneficial effect on CV health in overweight/obese youths.

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