A RXR Ligand 6-OH-11-O-Hydroxyphenanthrene with Antitumour Properties Enhances (−)-Epigallocatechin-3-gallate Activity in Three Human Breast Carcinoma Cell Lines

Farabegoli, Fulvia; Govoni, Marzia; Ciavarella, Carmen; Orlandi, Marina; Papi, Alessio

doi:10.1155/2014/853086

Cited by 11 publications

(27 citation statements)

References 45 publications

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“…MCF-7 cells resistant to tamoxifen (MCF-7TAM) were selected by growing MCF-7 cells in MEM medium without Phenol Red, containing 2 mM L-glutamine, 50 U/ml penicillin, 50 μg/ml streptomycin, 10 % FBS serum charcoal treated and 10 −7 M 4-OH-hydroxytamoxifen as previously described 17 [17]. In order to avoid any risk of contamination, the cell lines were assayed for oestrogen receptor α (ERα) expression by reverse transcription-PCR (RT-PCR) and immunoflurescence every 3 months: MCF-7 expressed ERα to a great extent, whereas MDA-MB-231 was completely devoid of ERα expression.…”

Section: Methodsmentioning

confidence: 99%

EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion

et al. 2017

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Epidermal growth factor receptor (EGFR) expression is an important marker in breast carcinoma pathology and is considered a pivotal molecule for cancer cell proliferation, invasion and metastasis. We investigated the effects of epigallocatechin-3-gallate (EGCG), the most active green tea catechin, in combination with 6-OH-11-O-hydroxyphenanthrene (IIF), a synthetic retinoid X receptor-γ (RXRγ) agonist, on three breast carcinoma cell lines: MCF-7, MCF-7TAM and MDA-MB-231. EGFR and AKT activation and molecular markers of cell motility and migration (CD44, extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMPs)) were studied after EGCG and IIF treatments. The EGCG + IIF treatment was the most active in down-regulating EGFR phosphorylation at Tyr1068 in all the investigated cell lines; p473AKT was also down-regulated in MCF-TAM cells. EGCG + IIF was also the most active treatment in reducing the expression of markers of invasion and migration in all the three cell lines: CD44, EMMPRIN, MMP-2 and -9 expression decreased, whereas TIMPs were up-regulated. Zymography and scratch assay also confirmed the reduced invasion tendency. We considered that EGCG and IIF treatments could alter the molecular network based on EGFR, CD44 and EMMPRIN expression interdependence and reduced the migration tendency in MCF-7, MCF-7TAM and MDA-MB-231 cells. These events only occurred in association with AKT inactivation in MCF-7TAM cells. In conclusion, the combination of EGCG and IIF significantly attenuated the invasive behaviour of breast carcinoma cells.

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Section: Methodsmentioning

confidence: 99%

EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion

et al. 2017

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“…We found that RARα protein expression nearly doubled in EGCG+IIF-treated samples ( Figure 1 B). RXR and particularly RXRγ are the main targets of IIF: as we found that RXRγ mRNA was hardly detectable (data not shown), we used a primer couple that is able to cover a homology region in RXRβ and γ genes, a strategy that we already applied elsewhere [ 12 ]. As expected, RXRα and βγ RNA expression augmented after IIF treatment and RXRγ protein expression increased significantly after all treatments ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Cells were seeded and after 18 h were placed in serum-free medium (D-MEM) with EGCG or IIF or both for 24 h. MMP2 and MMP9 activity was determined by gelatine zymography, as previously described [ 12 ]. The MMP activities, indicated by clear bands of gelatin digestion on a blue background, were quantified by using densitometric image analysis software (Image Lab Master, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Preclinical and clinical data support the use of single drugs inhibiting multiple molecular targets or combination therapies involving multiple drugs to achieve greater antineoplastic activity and overcome drug resistance [ 11 ]: inhibition of multiple signaling pathways is emerging as a new paradigm for anticancer treatment. Our previous studies on human carcinoma cell lines demonstrated that when the synthetic retinoid 6-OH-11-O-hydroxyphenanthrene (IIF) was associated with epigallocatechin-3-gallate (EGCG), the most active catechin being present in green tea, cytotoxicy increased and molecules that were related to invasion were downregulated [ 12 , 13 , 14 ]. IIF was more effective than ATRA in arresting cell growth and differentiation in neuroblastoma cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro

et al. 2018

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We conducted an in vitro study combining a rexinoid, 6-OH-11-O-hydroxyphenanthrene (IIF), and epigallocatechin-3-gallate (EGCG), which is the main catechin of green tea, on BE(2)-C, a neuroblastoma cell line representative of the high-risk group of patients. Neuroblastoma is the most common malignancy of childhood: high-risk patients, having N-MYC over-expression, undergo aggressive therapy and show high mortality or an increased risk of secondary malignancies. Retinoids are used in neuroblastoma therapy with incomplete success: the association of a second molecule might improve the efficacy. BE(2)-C cells were treated by EGCG and IIF, individually or in combination: cell viability, as evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was reduced, EGCG+IIF being the most effective treatment. Apoptosis occurred and the EGCG+IIF treatment decreased N-MYC protein expression and molecular markers of invasion (MMP-2, MMP-9 and COX-2). Zymography demonstrated nearly 50% inhibition of MMP activity. When BE(2)-C cells were grown in non-adherent conditions to enrich the tumor-initiating cell population, BE(2)-C-spheres were obtained. After 48 h and 72 h treatment, EGCG+IIF limited BE(2)-C-sphere formation and elicited cell death with a reduction of N-MYC expression. We concluded that the association of EGCG to IIF might be applied without toxic effects to overcome the incomplete success of retinoid treatments in neuroblastoma patients.

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“…In a recent study, we demonstrated that the combination of IIF and EGCG had a higher activity than the individual administration. IIF and EGCG can have a common signaling pathway that induces apoptosis by reducing epidermal growth factor receptor activation and its downstream kinase AKT-1 [75] .…”

Section: The New Rexinoid Iif Can Kill Bcscsmentioning

confidence: 99%

Role of nuclear receptors in breast cancer stem cells

Papi

Orlandi

2016

WJSC

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The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells, capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

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A RXR Ligand 6-OH-11-O-Hydroxyphenanthrene with Antitumour Properties Enhances (−)-Epigallocatechin-3-gallate Activity in Three Human Breast Carcinoma Cell Lines

Cited by 11 publications

References 45 publications

EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion

EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion

Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro

Role of nuclear receptors in breast cancer stem cells

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