Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway

Wang, Heyong; Wu, Chen; Wan, Shengbang; Zhang, Huijun; Zhou, Shunhua; Liu, Gentao

doi:10.1016/j.tox.2013.03.015

Cited by 45 publications

(36 citation statements)

References 54 publications

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“…Polyhydroxylated 1,4-naphthoquinones have also been isolated from sea urchins [19]. They are produced in large structural variety exhibiting diverse activities, for example, antimicrobial, antiviral, antifungal, anti-inflammatory, antimalarial, mutagenic, phytotoxic, insecticidal and recently extensively studied anticancer effects [20,21,22,23]. Another important feature of naturally produced naphthoquinones is their biotechnological potential.…”

Section: Introductionmentioning

confidence: 99%

Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

et al. 2015

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Four strains of the fungus Quambalaria cyanescens (Basidiomycota: Microstromatales), were used for the determination of secondary metabolites production and their antimicrobial and biological activities. A new naphthoquinone named quambalarine A, (S)-(+)-3-(5-ethyl-tetrahydrofuran-2-yliden)-5,7,8-trihydroxy-2-oxo-1,4-naphthoquinone (1), together with two known naphthoquinones, 3-hexanoyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone (named here as quambalarine B, 2) and mompain, 2,5,7,8-tetrahydroxy-1,4-naphthoquinone (3) were isolated. Their structures were determined by single-crystal X-ray diffraction crystallography, NMR and MS spectrometry. Quambalarine A (1) had a broad antifungal and antibacterial activity and is able inhibit growth of human pathogenic fungus Aspergillus fumigatus and fungi co-occurring with Q. cyanescens in bark beetle galleries including insect pathogenic species Beauveria bassiana. Quambalarine B (2) was active against several fungi and mompain mainly against bacteria. The biological activity against human-derived cell lines was selective towards mitochondria (2 and 3); after long-term incubation with 2, mitochondria were undetectable using a mitochondrial probe. A similar effect on mitochondria was observed also for environmental competitors of Q. cyanescens from the genus Geosmithia.

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Section: Introductionmentioning

confidence: 99%

Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

et al. 2015

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“…Mammalian cells contain three major classes of MaPKs: erK1/2, jnK, and p38. these molecules are important regulators of chemotaxis and/or random motility in a variety of cell types (28,(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

CCR7 regulates cell migration and invasion through MAPKs in metastatic squamous cell carcinoma of head and neck

Liu

Safdar

et al. 2014

International Journal of Oncology

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Migration and invasion of tumor cells are essential prerequisites for the formation of metastasis in malignant diseases. Previously, we have reported that CC chemokine receptor 7 (CCR7) regulates the mobility of squamous cell carcinoma of head and neck (SCCHN) cells through several pathways, such as integrin and cdc42. In this study, we investigated the connection between CCR7 and mitogen-activated protein kinase (MAPK) family members, and their influence on cell invasion and migration in metastatic SCCHN cells. Western blotting, immunostaining and fluorescence microcopy were used to detect the protein expression and distribution of MAPKs, and the Migration assay, Matrigel invasion assay and wound-healing assay to detect the role of MAPKs in CCR7 regulating cell mobility. To analyze the correlation between CCR7 and MAPK activity and clinicopathological factors immunohistochemical staining was emplyed. The results showed stimulation of CCL19 and the activation of CCR7 could induce ERK1/2 and JNK phosphorylation, while it had no efect on p38. After activation, ERK1/2 and JNK promoted E-cadherin low expression and Vimentin high expression. The MAPK pathway not only mediated CCR7 induced cell migration, but also mediated invasion speed. The immunohistochemistry results showed that CCR7 was correlated with the phosphorylation of ERK1/2 and JNK in SCCHN, and these molecules were all associated with lymph node metastasis. Therefore, our study demonstrates that MAPK members (ERK1/2 and JNK) play a key role in CCR7 regulating SCCHN metastasis.

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“…We have reported that lancemaside A, 20S-dihydroprotopanaxadiol, cinnamaldehyde, ceramide, chloroquine, and cynaropicrin are regarded as good modulators of CD29-mediated cell-cell adhesion [254647]. Others have found that ibrutinib (an orally active covalent BTK inhibitor) [48], shikonin [49], and biodentine [50] can inhibit the functional activation of integrins. Although there have been numerous attempts to develop CD29-function inhibitors with small molecules, none of these drugs has been released for clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion

Kim

Cho

2016

Korean J Physiol Pharmacol

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Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The β1-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.

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Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway

Cited by 45 publications

References 54 publications

Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

CCR7 regulates cell migration and invasion through MAPKs in metastatic squamous cell carcinoma of head and neck

Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion

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