Daurinol blocks breast and lung cancer metastasis and development by inhibition of focal adhesion kinase (FAK)

Woo, Jong Kyu; Jung, Hyun Jin; Park, Ji-Youn; Kang, Ju‐Hee; Lee, Byung Il; Shin, Dong Yun; Nho, Chu Won; Cho, Sooyoung; Seong, Je Kyung; Oh, Seung Hyun

doi:10.18632/oncotarget.18983

Cited by 18 publications

(5 citation statements)

References 63 publications

(57 reference statements)

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“…Earlier findings showed that FAK is responsible for coordination of cell motility and ECM remodeling during cancer cell invasion, and contributes to the secretion of matrix metalloproteinases [20]. The pharmacological inhibition of FAK phosphorylation was linked to reduced MMP-2 and MMP-9 expression and activation in breast and lung cancer cells [56]. Moreover, FAK was found to be crucial in promoting invasion and matrix metalloproteinases production in GBM [57,58].…”

Section: Discussionmentioning

confidence: 94%

Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo

Nešović

Rankov

Podolski-Renić

et al. 2020

Cancers

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Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood–brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.

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Section: Discussionmentioning

confidence: 94%

Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo

Nešović

Rankov

Podolski-Renić

et al. 2020

Cancers

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“…The pathway of focal adhesion has been extensively reported to be the most significant pathway in various diseases and signaling pathways as well. It regulates diverse cellular functions that were once activated by focal adhesion kinase (FAK), including adhesion, proliferation, migration, and survival [ 38 – 40 ]. A pattern of enhanced expression of FAK in lung carcinomas has been reported, which is related to nodal involvement and the deterioration of advanced disease stages [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the HOXA11 level in patients with lung squamous cancer and insights into potential molecular pathways via bioinformatics analysis

Zhang

Zhang²,

Zhai

et al. 2018

World J Surg Onc

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BackgroundThis study was carried out to discover the underlying role that HOXA11 plays in lung squamous cancer (LUSC) and uncover the potential corresponding molecular mechanisms and functions of HOXA11-related genes.MethodsTwenty-three clinical paired LUSC and non-LUSC samples were utilized to examine the level of HOXA11 using quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of HOXA11 was systematically analyzed based on 475 LUSC and 18 non-cancerous adjacent tissues from The Cancer Genome Atlas (TCGA) database. A total of 102 LUSC tissues and 121 non-cancerous tissues were available from Oncomine to explore the expressing profiles of HOXA11 in LUSC. A meta-analysis was carried out to further assess the differential expression of HOXA11 in LUSC, including in-house qRT-PCR data, expressing data extracted from TCGA and Oncomine databases. Moreover, the enrichment analysis and potential pathway annotations of HOXA11 in LUSC were accomplished via Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of hub genes and according correlations with HOXA11 were assessed to further explore the biological role of HOXA11 in LUSC.ResultsHOXA11 expression in LUSC had a tendency to be upregulated in comparison to adjacent non-cancerous tissues by qRT-PCR. TCGA data displayed that HOXA11 was remarkably over-expressed in LUSC compared with that in non-LUSC samples, and the area under curves (AUC) was 0.955 (P < 0.001). A total of 1523 co-expressed genes were sifted for further analysis. The most significant term enriched in the KEGG pathway was focal adhesion. Among the six hub genes of HOXA11, including PARVA, ILK, COL4A1, COL4A2, ITGB1, and ITGA5, five (with the exception of COL4A1) were significantly decreased compared with the normal lung tissues. Moreover, the expression of ILK was negatively related to HOXA11 (r = − 0.141, P = 0.002).ConclusionHigh HOXA11 expression may lead to carcinogenesis and the development of LUSC. Furthermore, co-expressed genes might affect the prognosis of LUSC.

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“…Daurinol (3) decreased the expression of focal adhesion kinase, which is hyper-activated and overexpressed in most solid tumors, but did not block the AKT pathway in both cell lines. Using a trans-well assay, daurinol (3) was found to inhibit migration and invasion (Woo et al 2017).…”

Section: Cytotoxic Activitiesmentioning

confidence: 99%

Arylnaphthalene lactones: structures and pharmacological potentials

2021

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Natural arylnaphthalene lactones are representative lignans that are found in various dietary and medicinal plants. Their unique structural features and significant pharmacological activity have attracted considerable attention from both synthetic and medicinal chemists. Owing to their unique structural features such as relative rigid tetracyclic skeleton, structural diversity of more than five substituents, and no chiral center, arylnaphthalene lactones are recognized as a valuable scaffold for drug discovery, in addition to their significant pharmacological activities. This review covers the structures and isolation of all naturally occurring arylnaphthalene lactone congeners reported. Based on the aryl substituents, they were categorized as Type I and Type II and further classified according to the oxidation state of the ring and glycosylation level. Special attention has been paid to natural arylnaphthalene lactones owing to their broad spectrum of biological activities such as cytotoxic, antiplatelet, antiviral, anti-HIV, antifungal, neuroprotective, and anti-inflammatory properties. All the products were reorganized based on their biological activities, and selected data are presented.

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Daurinol blocks breast and lung cancer metastasis and development by inhibition of focal adhesion kinase (FAK)

Cited by 18 publications

References 63 publications

Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo

Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo

Evaluation of the HOXA11 level in patients with lung squamous cancer and insights into potential molecular pathways via bioinformatics analysis

Arylnaphthalene lactones: structures and pharmacological potentials

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