Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells

Chen, Kunlun; Zhu, Pengfei; Chen, Wenhui; Luo, Kai; Shi, Xiaojing; Zhai, Wenlong

doi:10.18632/aging.203561

Cited by 33 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The oncostatic effects of melatonin through its pro-oxidant actions have been widely described [ 17 , 18 , 19 , 20 , 21 , 22 , 95 ]. Its mechanism of action, however, remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Various groups have, for many years, reported that high concentrations of melatonin can promote ROS generation, leading to cell death in a variety of cancers [ 17 , 18 , 19 , 20 , 21 , 22 ]; this suggests that melatonin can act as both an antioxidant and pro-oxidant in human cell lines, depending on the concentration and treatment duration. Furthermore, numerous studies have shown that melatonin enhances the cytotoxic effects of chemotherapeutic drugs on cancer cells, depending on the dose [ 23 ], thus suggesting that melatonin increases their chemotherapeutic effect [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

et al. 2022

View full text Add to dashboard Cite

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by ROS levels and by decreasing the capacity of the antioxidant system, leading to programmed cell death. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. Despite being widely recognized as a pro-oxidant molecule in tumor cells, the mechanism of action of melatonin remains unclear, which has hindered its use in clinical treatments. The current review aims to describe and clarify the proposed mechanism of action of melatonin inducing ROS production in cancer cells in order to propose future anti-neoplastic clinical applications.

show abstract

“…The oncostatic effects of melatonin through its pro-oxidant actions have been widely described [ 17 , 18 , 19 , 20 , 21 , 22 , 95 ]. Its mechanism of action, however, remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…PI3K-AKT signals are key and powerful suppressor for oxidative stress/ROS and conversely, ROS inhibits activation of PI3K. Furthermore, ROS induces ERS in DCMs, [ 31 – 34 , 36 , 37 , 45 ] and H19 indirectly activates PI3K by sponging miR-140-5p. Our results showed that H19 significantly increased the activation of PI3K and Nrf2 and thus decreased the expression of NOX-2/-4, as well as under high glucose conditions, and unfolded protein response’ proteins GRP-78/-94 and p-PERK and p-IRE1α, and these effects of H19 were corrected or rescued by PI3K inhibitor LY294002 ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis

Wang

Duan

Liao

et al. 2022

Aging

View full text Add to dashboard Cite

Objective: Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis. Methods: C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected. Results: H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosis in vivo . H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosis in vitro . Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT). Conclusion: H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.

show abstract

“…Further experimental studies demonstrated regression of gallbladder cancer by treatment with mTOR inhibitors (47). This was independent of the typhoid carrier state and was demonstrated to be mediated through PIK3CA/AKT/mTOR pathway (48)(49)(50)(51)(52). Although the single-phase I study of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity and failed to meet the objectives (53).…”

Section: Discussionmentioning

confidence: 99%

MAP Kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: Results from bioinformatic analysis of Next Generation Sequencing data from a hospital-based cohort

Rajput

Chigurupati

Purwar

et al. 2022

Preprint

View full text Add to dashboard Cite

BackgroundGallbladder Cancer (GBC) is one of the most common cancers of the biliary tract and the third commonest gastrointestinal (GI) malignancy worldwide. The disease is characterized by the late presentation and poor outcome despite treatment, and hence, newer therapies and targets need to be identified.MethodsThe current study investigated various functionally enriched pathways in GBC pathogenesis involving the genes identified through Next Generation Sequencing (NGS). The Pathway enrichment analysis and Gene Ontology (GO) were carried out after NGS, followed by the construction of the protein-protein interaction (PPI) network to discover associations among the genes.ResultsOf the thirty-three patients with GBC who were screened through next-generation sequencing (NGS), 27somatic mutations were identified. These mutations involved a total of 14 genes. The p53 and KRAS were commonly found to be mutated, while mutations in other genes were seen in one case each, the mean number of mutations were 1.2, and maximum mutation in a single case (eight) was seen in one case. The bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR, and Focal Adhesion PI3K-AKT-mTOR signaling pathways and cross-talk between these.ConclusionThe results suggest that the complex crosstalk between the mTOR, MAPK, and multiple interacting cell signaling cascades can promote GBC progression, and hence, mTOR - MAPK targeted treatment will be an attractive option.

show abstract

Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells

Cited by 33 publications

References 49 publications

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis

MAP Kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: Results from bioinformatic analysis of Next Generation Sequencing data from a hospital-based cohort

Contact Info

Product

Resources

About