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Lipoic acid-induced oxidative stress abrogates IGF-1R maturation by inhibiting the CREB/furin axis in breast cancer cell lines.
Farhat, D, Ghayad, SE, Icard, P, Le Romancer, M, Hussein, N, Lincet, H
Oncogene. 2020;(17):3604-3610
Abstract
The beneficial effects of lipoic acid (LA) in cancer treatment have been well documented in the last decade. Indeed, LA exerts crucial antiproliferative effects by reducing breast cancer cell viability, cell cycle progression and the epithelial-to-mesenchymal transition (EMT). However, the mechanisms of action (MOA) underlying these antiproliferative effects remain to be elucidated. Recently, we demonstrated that LA decreases breast cancer cell proliferation by inhibiting IGF-1R maturation via the downregulation of the proprotein convertase furin. The aim of the present study was to investigate the MOA by which LA inhibits furin expression in estrogen receptor α (ERα) (+) and (-) breast cancer cell lines. We unveil that LA exerts a pro-oxidant effect on these cell lines, the resulting reactive oxygen species (ROS) generated being responsible for the reduction in the expression of the major (CREB) protein. This transcription factor is overexpressed in many types of cancers and regulates the expression of furin in breast cancer cells independently of ERα, as evidenced herein by the inhibition of furin expression following CREB silencing. Consequently, our findings expose for the first time the complete MOA of LA via the CREB/furin axis leading to inhibition of breast cancer cell proliferation.
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Lipoic acid a multi-level molecular inhibitor of tumorigenesis.
Farhat, D, Lincet, H
Biochimica et biophysica acta. Reviews on cancer. 2020;(1):188317
Abstract
We discuss how lipoic acid (LA), a natural antioxidant, induces apoptosis and inhibits proliferation, EMT, metastasis and stemness of cancer cells. Furthermore, owing to its ability to reduce chemotherapy-induced side effects and chemoresistance, LA appears to be a promising compound for cancer treatment.
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Advances in synthesis of biotin and assembly of lipoic acid.
Cronan, JE
Current opinion in chemical biology. 2018;:60-66
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Abstract
Although biotin and lipoic acid are two universally conserved cofactors essential for intermediary metabolism, their synthetic pathways have become known only in recent years. Both pathways have unusual features. Biotin synthesis in Escherichia coli requires a methylation that is later removed whereas lipoic acid is assembled on the enzymes where it is required for activity by two different pathways.
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Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials.
Kucukgoncu, S, Zhou, E, Lucas, KB, Tek, C
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2017;(5):594-601
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Abstract
OBJECTIVES Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI). METHODS A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups. RESULTS Alpha-lipoic acid treatment coincided with a statistically significant 1.27 kg (confidence interval = 0.25 to 2.29) greater mean weight loss compared with the placebo group. A significant overall mean BMI difference of -0.43 kg/ m2 (confidence interval = -0.82 to -0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change. CONCLUSIONS Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.
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Advances in the management of diabetic neuropathy.
Várkonyi, T, Körei, A, Putz, Z, Martos, T, Keresztes, K, Lengyel, C, Nyiraty, S, Stirban, A, Jermendy, G, Kempler, P
Minerva medica. 2017;(5):419-437
Abstract
The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.
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Efficacy and safety of prostaglandin E1 plus lipoic acid combination therapy versus monotherapy for patients with diabetic peripheral neuropathy.
Jiang, DQ, Li, MX, Ma, YJ, Wang, Y, Wang, Y
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2016;:8-16
Abstract
The aim of this report was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) plus lipoic acid (LA) for the treatment of diabetic peripheral neuropathy (DPN) compared with that of PGE1 or LA monotherapy. Randomized controlled trials (RCT) published up to 3 August 2014 were reviewed. A random or fixed effect model was used to analyze outcomes expressed as risk ratios (RR) or mean difference (MD) with a 95% confidence interval (CI). I(2) statistic was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. The outcomes measured were as follows: clinical efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV and adverse effects. Thirty-one RCT with 2676 participants were included. Clinical efficacy of PGE1+LA combination therapy was significantly better than monotherapy (p<0.00001, RR=1.32, 95% CI 1.26 to 1.38). Compared with monotherapy, PGE1+LA combination therapy led to significant improvements in median MNCV (p<0.00001, MD=4.69, 95% CI 3.16 to 6.23), median SNCV (p<0.00001, MD=5.46, 95% CI 4.04 to 6.88), peroneal MNCV (p<0.00001, MD=5.19, 95% CI 3.71 to 6.67) and peroneal SNCV (p<0.00001, MD=5.50, 95% CI 3.30 to 7.70). There were no serious adverse events associated with drug intervention. PGE1+LA combination therapy is superior to PGE1 or LA monotherapy for improvement of neuropathic symptoms and nerve conduction velocities in patients with DPN. These findings should be further validated by larger well-designed and high-quality RCT.
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Emerging role of alpha-lipoic acid in the prevention and treatment of bone loss.
Roberts, JL, Moreau, R
Nutrition reviews. 2015;(2):116-25
Abstract
Osteoporosis is a chronic disease associated with decreased bone density that afflicts millions of people worldwide. Current pharmacological treatments are limited, costly, and linked to several negative side effects. These factors are driving current interest in the clinical use of naturally occurring bioactive compounds to mitigate bone loss. Alpha-lipoic acid, a potent antioxidant and essential member of mitochondrial dehydrogenases, has shown considerable promise as an antiosteoclastogenic agent due to its potent reactive oxygen species-scavenging capabilities along with a proven clinical safety record. Collectively, current data indicate that alpha-lipoic acid protects from bone loss via a 2-pronged mechanism involving inhibition of osteoclastogenic reactive oxygen species generation and upregulation of redox gene expression.
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Can α-lipoic acid mitigate progression of aging-related decline caused by oxidative stress?
Patel, MK, Riley, MA, Hobbs, S, Cortez-Cooper, M, Robinson, VJ
Southern medical journal. 2014;(12):780-7
Abstract
Aging is progressively deteriorating physiological function that leads to increasing risks of illness and death. Increases in life expectancy and the aging of a large segment of the population have made age-related disability and morbidity increasingly important issues. Supplements such as α-lipoic acid may have antiaging effects by positively affecting oxidative stress, cognitive function, and cardiovascular function.
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Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy.
Xu, Q, Pan, J, Yu, J, Liu, X, Liu, L, Zuo, X, Wu, P, Deng, H, Zhang, J, Ji, A
Diabetes research and clinical practice. 2013;(2):99-105
Abstract
AIMS: To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN). METHODS Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity. RESULTS Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment. CONCLUSIONS The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion.
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[Role of lipoic acid in health and disease].
Huk-Kolega, H, Skibska, B, Kleniewska, P, Piechota, A, Michalski, Ł, Goraca, A
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2011;(183):183-5
Abstract
Oxidative stress disturbs organism's homeostasis and leads to excessive reactive oxygen species (ROS) production. Researchers are still focused on antioxidants that help to reduce oxidative stress level and are helpful in treatment of diseases were ROS overproduction is observed. Among those antioxidants is lipoic acid (LA). When applied systemically LA accumulates in tissues and is converted to dihyrolipoic acid (DHLA) by lipoamide dehydrogenase. Both LA and DHLA are biologically active. LA scavenges hydroxyl radical, subchloric acid and singlet oxygen. Moreover, LA is able to chelate transient ions. Therefore, LA is used in diabetic nephropaties, fungi or heavy metal intoxication, liver diseases, neurodegenerative and cardiovascular diseases. This review surveys the antioxidant ability of LA and its role in pathological states where increased concentration of ROS is observed.