Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells

Ara, Carmen; Massimi, Mara; Devirgiliis, Laura Conti

doi:10.1007/pl00012503

Cited by 26 publications

(27 citation statements)

References 20 publications

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“…The modulation of cell-cell channel communication by RA occurs differently in these two experimental models: RA is able to revert cell transformation in Hep G2 cells, while in fetal hepatocytes, it may induce the expression of a more differentiated phenotype [24]. In this study, treatment with DADS significantly increased the GJIC of MGC803 cells, as was determined using the SLDT assay.…”

Section: Discussionmentioning

confidence: 55%

“…Gap junctional communication permits the direct exchange of small molecules and ions and has been implicated in tissue homeostasis/metabolite exchange. The lack of gap junctional intercellular communication (GJIC) plays important roles in the promotion and progression of carcinogenesis [24]. Intercellular communication is necessary in the control of cell growth and differentiation in multicellular organisms.…”

Section: Discussionmentioning

confidence: 99%

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Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

Ling¹,

Zhang²,

Qi³

et al. 2006

Cellular and Molecular Biology Letters

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Diallyl disulfide (DADS) is a major constituent of garlic. Previously, we found that DADS both inhibited proliferation in human gastric cancer cells in vitro and in vivo, and induced G2/M arrest. In this study, we investigated whether this differentiation effect was induced by DADS in human gastric cancer MGC803 cells, and whether it was related to an alteration in ERK activity. The results showed that the growth of MGC803 cells was inhibited by DADS. Cells treated with DADS displayed a lower nucleocytoplasmic ratio and tended to form gland and intercellular conjunction structures. The ConAmediated cell agglutination ratio and cells' ALP specific activity decreased. In MGC803 cells, dye transfer was limited to a few cells neighbouring the dyeinjected cell and to a depth of 1-2 layers beneath the scrape site. However, after treatment with DADS, the LY (Lucifer Yellow) was transferred to several cells immediately neighbouring the microinjected cell and to a depth of 2-4 cell layers from the scrape site. This indicated that DADS induced differentiation in MGC803 cells. Western blot analysis revealed that although DADS did not influence the quantity of ERK1/2 protein expressed, it did decrease its phosphorylation in a concentration-dependent manner, compared with the controls. At 30 mg·L -1 , DADS inhibited the activation of ERK1/2 in 15-30 min. These results suggested that the DADS-induced differentiation of MGC803 cells involved an alteration of the ERK1/2 signaling pathway.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

Ling¹,

Zhang²,

Qi³

et al. 2006

Cellular and Molecular Biology Letters

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“…It has been demonstrated that treatment of HepG2 cells with RA leads to an increase in the amount and phosphorylation of connexins, which also appear better localized on cell membranes and, hence, to enhanced gap junctional intercellular communication (5). It must be borne in mind that there is a certain interdependence in hepatocytes among the elements of gap and tight junctions, especially during their formation; connexins, for example, may play a role in modulating occludin expression (20).…”

Section: Discussionmentioning

confidence: 99%

Influence of Retinoic Acid on Adhesion Complexes in Human Hepatoma Cells: A Clue to Its Antiproliferative Effects

Ara

Devirgiliis

Massimi

2004

Cell Communication & Adhesion

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Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.

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“…43 Connexins can be regulated at both transcriptional and post-transcriptional levels. 23,44 Treatment with ATRA has been shown to increase Cx43 protein, mRNA or GJIC in a variety of cell lines, [22][23][24][45][46][47][48][49][50] however, it appears to have no effect or a decreased effect on Cx43 expression in other cell lines. 51,52 A potential explanation of this dual effect of ATRA treatment may be related to the dose-dependent nature of ATRA effects on cellular communication.…”

Section: Discussionmentioning

confidence: 99%

All-Trans Retinoic Acid Regulates Cx43 Expression, Gap Junction Communication and Differentiation in Primary Lens Epithelial Cells

Long

Bomser

Grzybowski

et al. 2010

Current Eye Research

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Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells

Cited by 26 publications

References 20 publications

Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

Influence of Retinoic Acid on Adhesion Complexes in Human Hepatoma Cells: A Clue to Its Antiproliferative Effects

All-Trans Retinoic Acid Regulates Cx43 Expression, Gap Junction Communication and Differentiation in Primary Lens Epithelial Cells

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