Evidence map›Paper›PMID 40474596›Full record

ArticleIntegrative cancer therapies

Holothurian Glycosaminoglycan (hGAG) Promoted Bim-Induced Apoptosis in Human Lung Adenocarcinoma A549 Cell Line Through Inhibition of Akt-Mediated FOXO3a Translocation.

Dai Hao-Yu, Liu Ting-Ting, Cao Yi-Wei, Sui Ai-Hua, Yang Xiao-Hui, Lin Cun-Zhi

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Article in Integrative cancer therapies. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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6 authors.

Dai Hao-YuThe Affiliated Hospital of Qingdao University, China.ORCID 0000-0001-8598-486X
Liu Ting-TingThe Affiliated Hospital of Qingdao University, China.
Cao Yi-WeiThe Affiliated Hospital of Qingdao University, China.
Sui Ai-HuaThe Affiliated Hospital of Qingdao University, China.
Yang Xiao-HuiThe Affiliated Hospital of Qingdao University, China.
Lin Cun-ZhiThe Affiliated Hospital of Qingdao University, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionHolothurian glycosaminoglycan (hGAG) is an extract from the body wall of sea cucumber and previous studies have proved many unique bioactivities of it, such as anti-tumor, anti-coagulation and immune regulation. Previous studies of our research group have shown hGAG promoted cell apoptosis in human lung adenocarcinoma A549 cells by upregulating Bax and caspase-3 and downregulating Bcl-2, indicating mitochondrial apoptosis pathway participated in the process. In the mitochondrial apoptosis pathway, Bim induces cell apoptosis by either direct activation of pro-apoptotic Bax/Bak or neutralization of anti-apoptotic Bcl-2 proteins. The transcription of Bim was regulated by FOXO3a. Akt, one of the most important cellular signaling molecules, regulates apoptosis through its phosphorylation. Phosphorylation of Akt results in translocation of FOXO3a from nuclear to cytoplasm. This study aimed to explore the mechanism by which hGAG induced apoptosis in A549 cells, focusing on its regulation of the Akt/FOXO3a/Bim signaling pathway.

methodsA549 cells were divided into three groups: control group, hGAG group and hGAG+SC79 (an Akt activator) group. Cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by flow cytometry. mRNA and protein expression levels were detected by Real-time Fluorescence Quantitative PCR and Western blotting assay, respectively. Protein localization was detected by immunofluorescence.

resultsThe results showed that hGAG induced apoptosis in A549 cells by downregulating p-Akt level, promoting FOXO3a expression, preventing FOXO3a nuclear export, and upregulating Bim expression, while SC79 reversed these effects, further demonstrating that hGAG regulated FOXO3a and Bim through inhibition of phosphorylation of Akt.

conclusionIn conclusion, our data demonstrated that hGAG promoted apoptosis in A549 cells via the Akt/FOXO3a/Bim-mediated intrinsic apoptosis pathway.

Indexed as

Adenocarcinoma of LungApoptosisBcl-2-Like Protein 11Forkhead Box Protein O3GlycosaminoglycansLung NeoplasmsProto-Oncogene Proteins c-aktA549 CellsAnimalsCell Line, TumorCell ProliferationHumansMitochondriaPhosphorylationSignal TransductionBCL2L11 protein, humanBcl-2-Like Protein 11Forkhead Box Protein O3FOXO3 protein, humanGlycosaminoglycansProto-Oncogene Proteins c-aktapoptosisBimforkhead box class o3aholothurian glycosaminoglycanlung cancer

Identifiers

PMID40474596
PMCPMC12144356

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