Zinc Alters Cytoskeletal Integrity and Migration in Colon Cancer Cells

Rudolf, Emil; Klvačová, Lada; John, Stanislav; Červinka, Miroslav

doi:10.14712/18059694.2017.8

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…The morphology of the MC3T3-E1 cells was round on both of the flat substrates (TC, non-patterned PDMS). In the case of motility, cells on TC did not exhibit a dose dependence on zinc, while migration of the MC3T3-E1 cells on flat PDMS was very sensitive to zinc concentration, similar to previous studies on cancer cell migration [ 39 , 40 , 42 ]. This suggests that the mode of migration on PDMS is fundamentally different than on TC for the pre-osteoblasts.…”

Section: Resultssupporting

confidence: 87%

“…In contrast, cell migration on flat PDMS was considerably faster (0.27–0.44 µm/min) and showed a steady decrease with increasing zinc concentration ( Figure 5 E). The migratory behavior of MC3T3-E1 cells on flat PDMS is similar to previous reports on breast cancer cells, where the addition of exogenous zinc also attenuated migration [ 39 , 40 ]. Motility of cells on both wide (0.29–0.34 µm/min) and narrow (0.28–0.36 µm/min) PDMS patterns was similar to that on flat PDMS, however zinc concentration did not have a significant effect ( Figure 5 E; p = 0.35–0.86).…”

Section: Resultssupporting

confidence: 87%

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The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part I (Migration)

et al. 2013

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Initial cell-surface interactions are guided by the material properties of substrate topography. To examine if these interactions are also modulated by the presence of zinc, we seeded murine pre-osteoblasts (MC3T3-E1, subclone 4) on micropatterned polydimethylsiloxane (PDMS) containing wide (20 µm width, 30 µm pitch, 2 µm height) or narrow (2 µm width, 10 µm pitch, 2 µm height) ridges, with flat PDMS and tissue culture polystyrene (TC) as controls. Zinc concentration was adjusted to mimic deficient (0.23 µM), serum-level (3.6 µM), and zinc-rich (50 µM) conditions. Significant differences were observed in regard to cell morphology, motility, and contact guidance. We found that cells exhibited distinct anisotropic migration on the wide PDMS patterns under either zinc-deprived (0.23 µM) or serum-level zinc conditions (3.6 µM). However, this effect was absent in a zinc-rich environment (50 µM). These results suggest that the contact guidance of pre-osteoblasts may be partly influenced by trace metals in the microenvironment of the extracellular matrix.

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Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 87%

The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part I (Migration)

et al. 2013

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“…Zn 2+ is an important regulator of the cytoskeleton in nucleated cells. 39 40 Zn 2+ regulates tubulin polymerization leading to nuclear transport of transcription factors in neuronal cells, 41 and has been shown to regulate the actin cytoskeleton, focal adhesion dynamics and cell migration in PC-3 and HeLa cells, 35 where Zn 2+ chelation supresses filopodia formation and results in the loss of stress fibres. Conversely, treatment with Py increased filopodia formation, supressed stress fibres and decreased the number and size of focal adhesions.…”

Section: Discussionmentioning

confidence: 99%

Agonist-Evoked Increases in Intra-Platelet Zinc Couple to Functional Responses

et al. 2018

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Background Zinc (Zn 2+ ) is an essential trace element that regulates intracellular processes in multiple cell types. While the role of Zn 2+ as a platelet agonist is known, its secondary messenger activity in platelets has not been demonstrated. Objectives This article determines whether cytosolic Zn 2+ concentrations ([Zn 2+ ] i ) change in platelets in response to agonist stimulation, in a manner consistent with a secondary messenger, and correlates the effects of [Zn 2+ ] i changes on activation markers. Methods Changes in [Zn 2+ ] i were quantified in Fluozin-3 (Fz-3)-loaded washed, human platelets using fluorometry. Increases in [Zn 2+ ] i were modelled using Zn 2+ -specific chelators and ionophores. The influence of [Zn 2+ ] i on platelet function was assessed using platelet aggregometry, flow cytometry and Western blotting. Results Increases of intra-platelet Fluozin-3 (Fz-3) fluorescence occurred in response to stimulation by cross-linked collagen-related peptide (CRP-XL) or U46619, consistent with a rise of [Zn 2+ ] i . Fluoresence increases were blocked by Zn 2+ chelators and modulators of the platelet redox state, and were distinct from agonist-evoked [Ca 2+ ] i signals. Stimulation of platelets with the Zn 2+ ionophores clioquinol (Cq) or pyrithione (Py) caused sustained increases of [Zn 2+ ] i , resulting in myosin light chain phosphorylation, and cytoskeletal re-arrangements which were sensitive to cytochalasin-D treatment. Cq stimulation resulted in integrin α IIb β 3 activation and release of dense, but not α, granules. Furthermore, Zn 2+ -ionophores induced externalization of phosphatidylserine. Conclusion These data suggest that agonist-evoked fluctuations in intra-platelet Zn 2+ couple to functional responses, in a manner that is consistent with a role as a secondary messenger. Increased intra-platelet Zn 2+ regulates signalling processes, including shape change, α IIb β 3 up-regulation and dense granule release, in a redox-sensitive manner.

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“…These findings could explain the presence of elevated Zn levels in secondary liver metastases compared with primary colorectal tissues. 21 Moreover, a recent study by Rudolf et al 22 has shown that Zn has the potential to be used in chemoprevention of advanced colorectal carcinoma. Zn may help suppress free radicals through metallothionein synthesis, act as an inhibitor of the nicotinamide adenine dinucleotide phosphate (reduced)-dependent lipid peroxidation, and prevent lipid peroxidation by inhibition of glutathione depletion.…”

Section: Discussionmentioning

confidence: 99%

Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

Lai¹,

Kuo

2016

Journal of Traditional and Complementary Medicine

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Sha Shen Mai Men Dong Tang (SMD-2; 沙參麥冬湯 shā shēn mài dōng tāng) is a Chinese medicinal herb (CMH; 中草藥 zhōng cǎo yào) used to treat symptoms associated with cancer therapy. The objective of this study was to assess the effect of SMD-2 on the levels of urinary copper (Cu), zinc (Zn), and selenium (Se) in lung cancer patients and head and neck cancer patients receiving chemoradiotherapy. Forty-two head and neck cancer patients and 10 lung cancer patients participated in our clinical trial. Each patient received chemoradiotherapy for 4 weeks. In addition, each patient was treated with SMD-2 for 8 weeks, including 2 weeks prior to and after the chemoradiotherapy treatment. Comparison of urinary Cu, Zn, and Se levels and the ratios of Zn to Cu and Se to Cu at three time points in the two types of cancer were assessed using the generalized estimating equations (GEEs). After the patients received chemoradiotherapy for 4 weeks, SMD-2 treatment was found to be associated with a significant decrease in urinary Cu levels, whereas urinary Zn and Se levels increased significantly. In addition, the ratios of Zn to Cu and Se to Cu in the urine samples of these patients also increased significantly. Both the urinary Zn levels and the ratio of Zn to Cu in head and neck cancer patients were significantly higher than in lung cancer patients. Urinary Zn and Se levels and the ratios of Zn to Cu and Se to Cu, but not urinary Cu levels, increased significantly during and after treatment when assessed using the GEE model. The SMD-2 treatments significantly increased Zn and Se levels in the urine of head and neck cancer patients. Increased Zn and Se levels in urine strengthened immune system.

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Zinc Alters Cytoskeletal Integrity and Migration in Colon Cancer Cells

Cited by 10 publications

References 16 publications

The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part I (Migration)

The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part I (Migration)

Agonist-Evoked Increases in Intra-Platelet Zinc Couple to Functional Responses

Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

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