H-7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells

Shabana, A.H.M.; Florescu-Zorila, Silvana; Lécolle, Sylvie; Goldberg, Michel; Forest, Nadine

doi:10.1002/(sici)1097-0029(19981101)43:3<233::aid-jemt5>3.0.co;2-l

Cited by 5 publications

(3 citation statements)

References 56 publications

(55 reference statements)

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“…Previous studies have reported a cytoplasmic distribution of DSP protein(s) in different pathological situations (for a review, see Refs. [13,33]). The studies suggest that the cytoplasmic localization of DSP protein(s) may be a consequence of the DSP overexpression with saturation of all desmosomal binding sites leading to cytoplasmic accumulation of the excess of protein [33] and that the cytoplasmic DSP particles may act as junction precursors [13].…”

Section: Discussionmentioning

confidence: 99%

“…[13,33]). The studies suggest that the cytoplasmic localization of DSP protein(s) may be a consequence of the DSP overexpression with saturation of all desmosomal binding sites leading to cytoplasmic accumulation of the excess of protein [33] and that the cytoplasmic DSP particles may act as junction precursors [13]. Similar data have been reported for other adhesion molecules, such as β-and γ-catenin [34].…”

Section: Discussionmentioning

confidence: 99%

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Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

et al. 2009

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“…H-7 (1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine), which inhibits several protein kinases including myosin light chain kinase (MLCK), Rho kinase, and protein kinases A and C, dramatically reduces actomyosindriven contractility, leading to cellular relaxation, deterioration of the microfilaments and perturbation of their membrane anchorage, and loss of stress fibers and focal contacts in various types of cultured cells. [14][15][16] Probably through these cytoskeletal modulations and related mechanisms, H-7 inhibits proliferation, migration, and EMT of several nontumor and tumor cell lines, [17][18][19] affects collagenase production and matrix metalloproteinase release in cultured human keratinocytes and airway smooth muscle cells, 20,21 and blocks wound healing in organ-cultured rat corneas. 22 Based on these findings, we hypothesize that H-7 might reduce the incidence and/or severity of secondary cataract after lens surgery.…”

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confidence: 99%

Effect of H-7 on Secondary Cataract After Phacoemulsification in the Live Rabbit Eye

Tian

Heatley

Filla

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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Purpose: This study is aimed to determine if the serine-threonine kinase inhibitor H-7 inhibits secondary cataract after phacoemulsification in the live rabbit eye. Methods: Eighteen rabbits underwent extracapsular lens extraction by phacoemulsification in 1 eye. The eye was treated with intravitreal H-7 (300 or 1,200 mM; n ¼ 6 or 5) or balanced salt solution (BSS) (n ¼ 7) immediately after the surgery and twice weekly for 10 weeks. Each eye received slit lamp biomicroscopy once a week, during which posterior capsule opacification (PCO) was evaluated. The eye was then enucleated and the lens capsule was prepared, fixed, and imaged. PCO was evaluated again on the isolated lens capsule under a phase microscope. Soemmering's ring area (SRA) and the entire lens capsule area were measured from capsule images on a computer and the percentage of SRA (PSRA) in the entire capsule area was calculated. Wet weight of the capsule (WW) was determined on a balance. Results: No significant difference in PCO was observed in any comparison. No significant differences in SRA, PSRA, and WW were observed between the 300 mM H-7-treated eye and the BSS-treated eye. However, SRA, PSRA, and WW in the 1,200 mM H-7-treated eye were significantly smaller than those in the BSS-treated eye [28.3 AE 16.2 vs. 61.4 AE 8.86 mm 2 (P ¼ 0.001), 33% AE 20% vs. 65% AE 15% (P ¼ 0.01), and 65.6 AE 27.9 vs. 127.0 AE 37.3 mg (P ¼ 0.01)]. Conclusions: Intravitreal H-7 (1,200 mM) significantly inhibits Soemmering's ring formation in the live rabbit eye, suggesting that agents that inhibit the actomyosin system in cells may prevent secondary cataract after phacoemulsification.

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Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro

Sureshkumar¹,

Haripriya

Muthukkaruppan³

et al. 2011

Graefes Arch Clin Exp Ophthalmol

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Background To determine whether the cytoskeletal drugs H-7 and Latrunculin B (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens capsular bag. Methods Following extracapsular cataract (lens) extraction in human donor eyes, the capsular bag was prepared and cultured by standard techniques. Forty-eight capsular bags were studied, in which 13 were treated with H-7 (50, 100 or 300μM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10μM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular bags were from paired eyes of 20 donors with 1 bag being treated with H-7/LAT-B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal drug/vehicle was replaced every 3–4 days for 4 weeks. PCO was assessed daily using inverted phase-contrast microscopy and scored on a 4-point scale. Results In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the anterior capsule migrated to and proliferated on the posterior capsule by 3–7 days and apparent LEC growth on the posterior capsule with severe capsular wrinkling (PCO Grade 3) was seen by 2-3weeks. When treated continuously with H-7 or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were inhibited in a dose-dependent manner, with the inhibition being complete (PCO Grade 0) in the 300μM H-7 (n=8, p<0.001) or 10μM LAT-B culture (n=3, p=0.002). Conclusion H-7 and LAT-B dose-dependently inhibited PCO formation in the cultured human lens capsular bags, suggesting that cytoskeletal drugs might prevent PCO formation after surgery in the human eye.

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H-7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells

Cited by 5 publications

References 56 publications

Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

Effect of H-7 on Secondary Cataract After Phacoemulsification in the Live Rabbit Eye

Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro

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