α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation

Yang, Lan; Wen, Ya; Lv, Guorong; Lin, Yuntao; Tang, Junlong; Lu, Jingxiao; Zhang, Manqiao; Liu, Wen; Sun, Xiaojuan

doi:10.1016/j.bbrc.2017.10.030

Cited by 24 publications

(16 citation statements)

References 22 publications

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“…Fredericks and Ren, 2013). Recently, its tumor-promoting effects were shown in many malignancies including lung cancer (Yang et al, 2017a;Jiang et al, 2018;Mitra et al, 2018;Wang and Wang, 2020), gastric cancer (Ye et al, 2018), colorectal cancer (Ding et al, 2019), ovarian carcinoma (Huang et al, 2018), renal cell carcinoma (Gu et al, 2017), breast cancer (Lim et al, 2000;Haines et al, 2014;López-Cortés et al, 2020), and esophageal squamous cell carcinoma (Shi et al, 2018). In addition, in lung cancer (Chen et al, 2020), ovarian cancer (Xu et al, 2018), colorectal cancer (Agrawal et al, 2019), and breast cancer (Chen et al, 2018), its associations with the resistance of the tumors to chemotherapeutic drugs were presented, and its downregulation could reverse the resistant status or enhance the sensitivity to the drugs, indicating its potential as a chemotherapeutic target in the malignancies.…”

Section: Discussionmentioning

confidence: 99%

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Zhang

Gao

et al. 2020

Front. Genet.

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Karyopherin α2 (KPNA2) was reported to be overexpressed and have unfavorable prognostic effects in many malignancies including hepatocellular carcinoma (HCC). Although its contributions to inflammatory response were reported in many studies, its specific associations with immune infiltrations and immune pathways during cancer progression were unclear. Here, we aimed to identify new markers for HCC diagnosis and prognosis through KPNA2-associated immune analyses. RNA-seq expression data of HCC datasets were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. The gene expressions were counts per million normalized. The infiltrations of 24 kinds of immune cells in the samples were evaluated with ImmuCellAI (Immune Cell Abundance Identifier). The Spearman correlations of the immune infiltrations with KPNA2 expression were investigated, and the specific positive correlation of B-cell infiltration with KPNA2 expression in HCC tumors was identified. Fifteen genes in KEGG (Kyoto Encyclopedia of Genes and Genomes) B-cell receptor signaling pathway presented significant correlations with KPNA2 expression in HCC. Among them, GRB2 and NRAS were indicated to be independent unfavorable prognostic factors for HCC overall survival. Clinical Proteomic Tumor Analysis Consortium HCC dataset was investigated to validate the results at protein level. The upregulation and unfavorable prognostic effects of KPNA2 and GRB2 were confirmed, whereas, unlike its mRNA form, NRAS protein was presented to be downregulated and have favorable prognostic effects. Through receiver operating characteristic curve analysis, the diagnostic potential of the three proteins was shown. The RNA-binding proteins (RBPs) of KPNA2, NRAS, and GRB2, downloaded via The Encyclopedia of RNA Interactomes, were investigated for their clinical significance in HCC at protein level. An eight-RBP signature with independent prognostic value and dysregulations in HCC was identified. All the RBPs were significantly correlated with MKI67 expression and at least one of KPNA2, GRB2, and NRAS at protein level in HCC, indicating Zhang et al. KPNA2-Associated Immune Analyses in HCC Frontiers in Genetics | www.frontiersin.org 2 October 2020 | Volume 11 | Article 593273 their roles in HCC progression and the regulation of the three proteins. We concluded that KPNA2, GRB2, NRAS, and their RBPs might have coordinating roles in HCC immunoregulation and progression. They might be new markers for HCC diagnosis and prognosis predication and new targets for HCC immunotherapy.

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Section: Discussionmentioning

confidence: 99%

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Zhang

Gao

et al. 2020

Front. Genet.

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“…In the same study, it was also found that ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells [73]. In lung cancer cells, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation [74].…”

Section: α-Lipoic Acid Pharmacological Activities: An Overviewmentioning

confidence: 99%

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

et al. 2019

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α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.

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“…Regulated kinase ERK1/2 is concerned with cell survival while terminal kinase c-Jun-NH2 is involved in induction of apoptosis thus; ERK1/2 antagonist led to significant apoptosis since; ERK1/2 has anti-apoptotic property. Therefore, the molecular effect of thioctic acid during doxorubicininduced cardiotoxicity is activation of anti apoptotic pathway and inhibition of apoptotic pathway [35].…”

Section: Apoptosismentioning

confidence: 99%

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OAJOM

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α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation

Cited by 24 publications

References 22 publications

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

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