Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition

Peng, Peipei; Zhang, Xiaojin; Qi, Tao; Cheng, Hao; Kong, Qiuyue; Liu, Li; Cao, Xiaofei; Ding, Zhengnian

doi:10.1002/2211-5463.12820

Cited by 26 publications

(21 citation statements)

References 30 publications

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“…This hypothesis was confirmed by adult mice knocked-out of essential autophagy genes that demonstrated decreased proliferation of cancer cells and increased tumor cell death of lung adenocarcinoma [ 198 ]. Consistently, human lung adenocarcinoma specimens showed increased autophagy compared to the matched normal lung tissues [ 199 ].…”

Section: Autophagy In Specific Tumor Typesmentioning

confidence: 86%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.

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Section: Autophagy In Specific Tumor Typesmentioning

confidence: 86%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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“…The antioxidant effects of ascorbic acid and liposomal ALA as an adjuvant in cancer treatment were recently re-stated [66][67][68] in ovarian carcinoma cells [69], human breast cells [70,71], non-small lung cancer cells [72], human colon cancer cells [73] or hepatoma cells [74].…”

Section: Ala and Cancermentioning

confidence: 99%

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

Pop

Crișan²,

Barca

et al. 2021

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Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f2 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f2 = 31.6); the optimal profile was obtained for Formula #4 (f2 = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.

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“…Activation of the AMPK/mTOR signaling pathway can induce POI by triggering the autophagy of theca-interstitial cells [52]. Moreover, ALA exerts an anti-lung cancer cell growth effect through mTOR-mediated inhibition of autophagy [53]. However, the effect of ALA on mTORrelated pathways in POI requires further validation.…”

Section: Molecular Dockingmentioning

confidence: 99%

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha-lipoic acid on primary ovarian insufficiency

Kong¹,

Cho²,

Lee³

et al. 2022

Preprint

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Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha-lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Protein-Protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein-to-protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top ten hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple-targets and multiple-pathways mechanisms.

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Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition

Cited by 26 publications

References 30 publications

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha-lipoic acid on primary ovarian insufficiency

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