Inhibitory effects of retinoic acid and IIF on growth, migration and invasiveness in the U87MG human glioblastoma cell line

Papi, Alessio; Bartolini, G; Ammar, K.; Guerra, Francesco; Ferreri, Anna Maria; Rocchi, Paola; Orlandi, Marina

doi:10.3892/or.18.4.1015

Cited by 19 publications

(28 citation statements)

References 35 publications

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“…These results indicate that ATRA may also regulate the migration and invasion of glioma cells using alternate mechanisms. Previous studies have reported that ATRA can inhibit the activity of MMP-2 (20) and MMP-9 (15) via tissue inhibitor of metalloproteinase, a protein that may be involved in the regulation of migration and invasion of ATRA-treated glioma cells.…”

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

2015

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Abstract. All-trans retinoic acid (ATRA) is a derivative of vitamin A that can induce differentiation and apoptosis, as well as inhibit proliferation, in glioma cells. However, the effect of ATRA on the migration and invasiveness of glioma remains poorly understood. In addition, although it is universally accepted that ATRA can induce apoptosis and inhibit proliferation in glioma cells, the association between the concentration and effects of ATRA remain unclear. Therefore, the present study investigated the effects of ATRA treatment on the migration, invasion, apoptosis and proliferation of glioma cells. The U87 and SHG44 glioma cell lines were treated with various concentrations of ATRA, consisting of 0, 5, 10, 20 and 40 µmol/l. A scratch wound healing assay and a Matrigel invasion assay were used to investigate cell migration and invasion, respectively. Flow cytometry was performed to investigate apoptosis and cell cycle distribution. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression of matrix metalloproteinase (MMP)-2 and -9 in each cell treatment group. Following treatment with ATRA, the migration, invasion and proliferation of the glioma cells were significantly inhibited, and the apoptosis rate was significantly increased compared with that of the blank control group. Furthermore, a dose-effect association was identified between each effects and ATRA treatment. The mRNA and protein expression of MMP-2 in U87 glioma cells was not significantly affected following treatment with low concentrations of ATRA, consisting of 5 and 10 µmol/l ATRA, compared with the expression in the control group (P>0.05). However, treatment with high concentrations of ATRA, consisting of 20 and 40 µmol/l ATRA, significantly downregulated the expression levels of MMP-2 in U87 cells. In contrast to U87 cells, the administration of ATRA treatment to SHG44 glioma cells resulted in a significant and dose-dependent downregulation in MMP-2 mRNA and protein expression (P<0.01). In addition, significant downregulation of MMP-9 expression was identified in the two glioma cell lines (P<0.01). The results of the present study indicate that treatment with ATRA may inhibit migration, invasion and proliferation, and promote apoptosis in glioma cells. Furthermore, the current study indicates that the inhibition of glioma cell invasion by ATRA may be partially associated with its effect ability to downregulate MMP expression.

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Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

2015

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“…This finding recalls recent data showing that RXR ligands are endowed with higher antitumor efficacy compared with RAR ligands. 23 Such molecules selectively target tumor cells without inducing the typical in vivo side effects of retinoids. 21,38 Moreover, we found that PGZ, a ligand of PPARg, is the least active molecule among the NR agonists tested, thus showing that NRs agonists are not interchangeable in their potential biological activity on breast CSCs.…”

Section: Discussionmentioning

confidence: 99%

“…20 6-OH-11-Ohydroxyphenanthrene (IIF) is a recently developed RXR ligand that activates the retinoid X response element (RXRE) and exerts higher antitumor effects compared with RA without measurable side effects. [21][22][23] The RAR ligand RA activates the retinoic acid response element (RARE), which function is mediated by RAR homodimers, as well as by RAR-RXR heterodimers. 20 RXR receptors regulate gene expression by forming heterodimers with peroxisome proliferator activated receptors (PPAR a, b and g).…”

Section: Introductionmentioning

confidence: 99%

Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells

et al. 2012

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Recent literature highlights the importance of pro-inflammatory cytokines in the biology of breast cancer stem cells (CSCs), unraveling differences with respect to their normal counterparts. Expansion of mammospheres (MS) is a valuable tool for the in vitro study of normal and cancer mammary gland stem cells. Here, we expanded MSs from human breast cancer and normal mammary gland tissues, as well from tumorigenic (MCF7) and non-tumorigenic (MCF10) breast cell lines. We observed that agonists for the retinoid X receptor (6-OH-11-O-hydroxyphenanthrene), retinoic acid receptor (all-trans retinoic acid (RA)) and peroxisome proliferator-activated receptor (PPAR)-c (pioglitazone (PGZ)), reduce the survival of MS generated from breast cancer tissues and MCF7 cells, but not from normal mammary gland or MCF10 cells. This phenomenon is paralleled by the hampering of pro-inflammatory Nuclear Factor-jB (NF-jB)/Interleukin-6 (IL6) axis that is hyperactive in breast cancer-derived MS. The hindrance of such pathway associates with the downregulation of MS regulatory genes (SLUG, Notch3, Jagged1) and with the upregulation of the differentiation markers estrogen receptor-a and keratin18. At variance, the PPARa agonist Wy14643 promotes MS formation, upregulating NF-jB/IL6 axis and MS regulatory genes. These data reveal that nuclear receptors agonists (6-OH-11-O-hydroxyphenanthrene, RA, PGZ) reduce the inflammation dependent survival of breast CSCs and that PPARa agonist Wy14643 exerts opposite effects on this phenotype.

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“…Current therapeutic strategies for glioblastoma include surgery, radiation therapy and chemotherapy. However, the median survival of glioblastoma patients is extremely poor (3).…”

Section: Introductionmentioning

confidence: 99%

Hexane extract from Sargassum serratifolium inhibits the cell proliferation and metastatic ability of human glioblastoma U87MG cells

et al. 2015

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Abstract. The present study is the first to demonstrate the anticancer effects of a hexane extract from the brown algae Sargassum serratifolium (HES) on human cancer cell lines, including glioblastoma U87MG, cervical cancer HeLa and gastric cancer MKN-28 cells, as well as liver cancer SK-HEP 1 cells. Among these cancer cell lines, U87MG cells were most sensitive to the cell death induced by HES. HES exhibited a cytotoxic effect on U87MG cells at concentrations of 14-16 µg/ml, yet an effect was not observed in human embryonic kidney HEK293 cells. The antiproliferative effects of HES were regulated by inhibition of the MAPK/ERK signaling pathway which plays a pivotal role in the proliferation of glioblastoma U87MG cells. In addition, treatment with HES led to cell morphological changes and cell cytoskeleton degradation through regulation of actin dynamic signaling. Furthermore, migration and invasion of the U87MG cells were inhibited by HES via suppression of matrix metalloproteinase (MMP)-2 and -9 expression. Thus, our results suggest that HES is a potential therapeutic agent which has anticancer effects on glioblastoma.

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Inhibitory effects of retinoic acid and IIF on growth, migration and invasiveness in the U87MG human glioblastoma cell line

Cited by 19 publications

References 35 publications

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells

Hexane extract from Sargassum serratifolium inhibits the cell proliferation and metastatic ability of human glioblastoma U87MG cells

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