Therapeutic potential of AMPK signaling targeting in lung cancer: Advances, challenges and future prospects

Ashrafizadeh, Milad; Mirzaei, Sepideh; Hushmandi, Kiavash; Rahmanian, Vahid; Zabolian, Amirhossein; Raei, Mehdi; Farahani, Mahdi Vasheghani; Goharrizi, Mohammad Ali Sheikh Beig; Khan, Haroon; Zarrabi, Ali; Samarghandian, Saeed

doi:10.1016/j.lfs.2021.119649

Cited by 45 publications

(18 citation statements)

References 246 publications

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“…Most NSCLC patients have advanced disease at diagnosis. Platinum-based chemotherapy doublet, including antimicrotubule agents (e.g., paclitaxel/carboplatin and docetaxel/cisplatin), is the standard of care for first-line treatment of advanced NSCLC [3][4][5]. However, only partial responses were achieved with this approach in 30% to 40% of patients [6].…”

Section: Introductionmentioning

confidence: 99%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

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The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.

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Section: Introductionmentioning

confidence: 99%

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

et al. 2022

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“…The expression level of Tufm in lung cancer tissues has been shown to be positively correlated with epithelial cell marker protein E-cadherin and negatively correlated with the progression of lung cancer. Knockdown of Tufm inhibited the expression of mitochondrial gene-encoded proteins in lung cancer cells, causing impairment of mitochondrial function and promoting ROS production ( 36 ). The cellular energy and oxidative stress caused by Tufm downregulation can lead to the activation of AMP-activated protein kinase (AMPK).…”

Section: Discussionmentioning

confidence: 99%

Effects of short-term waterfall forest aerosol air exposure on rat lung proteomics

Zhu¹,

Zhao²,

Zhu³

et al. 2022

Ann Transl Med

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Background: Chronic exposure to airborne microparticles has been shown to increase the incidence of several chronic diseases. Previous studies have found that waterfall forest aerosols contribute to a diminished immune stress response in patients with asthma. However, the specific effects of short-term waterfall forest aerosol exposure on lung proteins have not been fully elucidated.Methods: This study used liquid chromatography-tandem mass spectrometry (LC-MS) to analyze changes in protein expression in the lungs of rats exposed to short-term waterfall forest aerosol environments. Specific protein markers were identified using bioconductivity analysis screening and validated using immunohistochemistry.Results: Waterfall forest aerosol environment exposure on day 5 downregulated the expression of the classical inflammatory pathway nuclear factor κB (NF-κB) signaling pathway. As the waterfall forest aerosol environment increased due to the duration of exposure, it was involved in oxidative phosphorylation and then hormone signaling in lung cells from the very beginning. In contrast, at day 15 of exposure, there is an effect on the regulation of the immune-related high-affinity IgE receptor pathway. In addition, iron-sulfur Rieske protein (Uqcrfs1), mitochondrial Tu translation elongation factor (Tufm) and ribosomal protein L4 (Rpl4) were identified as possible bioindicators for the evaluation of air quality.Conclusions: These results provide a comprehensive proteomic analysis that supports the positive contribution of a good air quality environment to lung health.

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“…These parts that do not encode proteins are known as noncoding RNAs and miRNA, lncRNA, and circRNA belong to this group (Pandya et al, 2020). These RNA molecules show regulatory functions in the cells and their aberrant expression has been found in the various tumors (Abadi, Zarrabi et al, 2021; Ashrafizadeh, Ahmadi, Mohammadinejad et al, 2020; Ashrafizadeh, Mirzaei, Hushmandi et al, 2021; Ashrafizadeh, Shahinozzaman et al, 2021; Chen et al, 2019; Z. Ma et al, 2019; Paskeh, Mirzaei, Orouei et al, 2021). Furthermore, circRNAs and lncRNAs regulate miRNA expression via sponging (Chen et al, 2019; Chew et al, 2018; Kirtonia et al, 2021; Mirzaei, Paskeh et al, 2021).…”

Section: Ncrnas In Nf‐κb/emt Regulationmentioning

confidence: 99%

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Mirzaei

Saghari

Bassiri

et al. 2022

Journal Cellular Physiology

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101

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Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial‐to‐mesenchymal transition (EMT) is a well‐known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor‐kappaB (NF‐κB) is one of them. The nuclear translocation of NF‐κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF‐κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF‐κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor‐β, and Slug as inducers of EMT undergo upregulation by NF‐κB to promote metastasis of tumor cells. After EMT induction driven by NF‐κB, a significant decrease occurs in E‐cadherin levels, while N‐cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF‐κB/EMT axis in cancers. Moreover, NF‐κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF‐κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.

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Therapeutic potential of AMPK signaling targeting in lung cancer: Advances, challenges and future prospects

Cited by 45 publications

References 246 publications

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems

Effects of short-term waterfall forest aerosol air exposure on rat lung proteomics

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

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