Effect of tamoxifen and fulvestrant long-term treatments on ROS production and (pro/anti)-oxidant enzymes mRNA levels in a MCF-7-derived breast cancer cell line

Badia, Eric; Moréna, Marion; Lauret, Céline; Boulahtouf, Abdelhay; Boulle, Nathalie; Cavaillès, Vincent; Balaguer, Patrick; Cristol, Jean Paul

doi:10.1007/s12282-015-0626-7

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…As ERα expression is lost or decreased in OHTR cells (Al Saleh et al ., ), we next asked whether breast cancer cell resistance to OHTam could be associated with changes in HDAC9 gene expression. Comparison of the HDAC mRNA profile in previously described MCF7 cell lines that are responsive or resistant to OHTam (Badia et al ., , ) showed that among the 11 HDACs analyzed, only HDAC9 expression was significantly higher (7.6 times) in OHTR than in parental OHTam‐responsive cells (Fig. A).…”

Section: Resultsmentioning

confidence: 93%

“…Similar results were obtained with OHTR T47D (Mishra et al ., ) (Fig. B) as well as in other MCF7 cell lines (Brünner et al ., ; Eric Badia et al ., ; Gonzalez‐Malerva et al ., ) (Fig. A,B).…”

Section: Resultsmentioning

confidence: 99%

“…The MCF7 breast cancer cell line was obtained from the American Type Culture Collection (LGC Standards, Molsheim, France) and was grown using the recommended culture conditions. The OHTam‐resistant MCF7 (MCF7‐OHTR) cell lines have been described previously (Brünner et al ., ; Badia et al ., ; Eric Badia et al ., ) and were authenticated by PCR‐single‐locus technology (Eurofins, Ebersberg, Germany). T47D TamR cells were recently described elsewhere (Mishra et al ., ).…”

Section: Methodsmentioning

confidence: 99%

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Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers

et al. 2019

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Estrogens play a pivotal role in breast cancer etiology, and endocrine therapy remains the main first line treatment for estrogen receptor‐alpha ( ER α)‐positive breast cancer. ER are transcription factors whose activity is finely regulated by various regulatory complexes, including histone deacetylases (HDACs). Here, we investigated the role of HDAC 9 in ER α signaling and response to antiestrogens in breast cancer cells. Various Michigan Cancer Foundation‐7 ( MCF 7) breast cancer cell lines that overexpress class II a HDAC 9 or that are resistant to the partial antiestrogen 4‐hydroxy‐tamoxifen (OHTam) were used to study phenotypic changes in response to ER ligands by using transcriptomic and gene set enrichment analyses. Kaplan–Meier survival analyses were performed using public transcriptomic datasets from human breast cancer biopsies. In MCF 7 breast cancer cells, HDAC 9 decreased ER α mRNA and protein expression and inhibited its transcriptional activity. Conversely, HDAC 9 mRNA was strongly overexpressed in OHT am‐resistant MCF 7 cells and in ER α‐negative breast tumor cell lines. Moreover, HDAC 9‐overexpressing cells were less sensitive to OHT am antiproliferative effects compared with parental MCF 7 cells. Several genes (including MUC 1, SMC 3 and S100P) were similarly deregulated in OHT am‐resistant and in HDAC 9‐overexpressing MCF 7 cells. Finally, HDAC 9 expression was positively associated with genes upregulated in endocrine therapy‐resistant breast cancers and high HDAC 9 levels were associated with worse prognosis in patients treated with OHT am. These results demonstrate the complex interactions of class II a HDAC 9 with ER α signaling in breast cancer cells and its effect on the response to hormone therapy.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers

et al. 2019

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“…Moreover, the ROS is the major risk factor for the development and progression of breast cancer. To determine the antioxidant potential of the formulation, levels of ROS were estimated by using the 2,7-Dichlorofloresin diacetate (DCFDA) method [ 58 ]. This was performed in a 96-well culture plate seeded with 2 × 10 5 MCF 7 cells/well.…”

Section: Methodsmentioning

confidence: 99%

Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer

et al. 2022

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The solid self-nanoemulsifying drug delivery system (s-SNEDDS) is a growing platform for the delivery of drugs via oral route. In the present work, tamoxifen (TAM) was loaded in SNEDDS with resveratrol (RES), which is a potent chemotherapeutic, antioxidant, anti-inflammatory and P-gp inhibitor for enhancing bioavailability and to obtain synergistic anti-cancer effect against breast cancer. SNEDDS were developed using capmul MCM as oil, Tween 80 as surfactant and transcutol-HP as co-surfactant and optimized by central composite rotatable design. Neusilin US2 concentration was optimized for adsorption of liquid SNEDDS to prepare s-SNEDDS. The developed formulation was characterized and investigated for various in vitro and cell line comparative studies. Optimized TAM-RES-s-SNEDDS showed spherical droplets of a size less than 200 nm. In all in vitro studies, TAM-RES-s-SNEDDS showed significantly improved (p ˂ 0.05) release and permeation across the dialysis membrane and intestinal lumen. Moreover, TAM-RES-s-SNEDDS possessed significantly greater therapeutic efficacy (p < 0.05) and better internalization on the MCF-7 cell line as compared to the conventional formulation. Additionally, oral bioavailability of TAM from SNEDDS was 1.63 folds significantly higher (p < 0.05) than that of combination suspension and 4.16 folds significantly higher (p < 0.05) than TAM suspension. Thus, findings suggest that TAM- RES-s-SNEDDS can be the future delivery system that potentially delivers both drugs to cancer cells for better treatment.

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“…Tamoxifen’s main application is the treatment and/or prevention of breast cancer most frequently occurring among post-menopausal women, but this drug proved to be applicable for the treatment of infertility both in women and men [ 2 , 3 ], or for the prevention of gynecomastia [ 4 ]. Aside from Tamoxifen’s SERM activity explored in the indications listed above, its function in the generation of Reactive Oxygen Species (ROS) is also well-documented concerning adverse effects [ 3 , 5 ]. ROS including, e.g., superoxide anion and hydroxyl radicals, are involved in signal transmission pathways regulating cell growth, differentiation, survival, inflammation and immune response.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

et al. 2022

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Utilizing McMurry reactions of 4,4′-dihydroxybenzophenone with appropriate carbonyl compounds, a series of 4-Hydroxytamoxifen analogues were synthesized. Their cytotoxic activity was evaluated in vitro on four human malignant cell lines (MCF-7, MDA-MB 231, A2058, HT-29). It was found that some of these novel Tamoxifen analogues show marked cytotoxicity in a dose-dependent manner. The relative ROS-generating capability of the synthetized analogues was evaluated by cyclic voltammetry (CV) and DFT modeling studies. The results of cell-viability assays, CV measurements and DFT calculations suggest that the cytotoxicity of the majority of the novel compounds is mainly elicited by their interactions with cellular targets including estrogen receptors rather than triggered by redox processes. However, three novel compounds could be involved in ROS-production and subsequent formation of quinone-methide preventing proliferation and disrupting the redox balance of the treated cells. Among the cell lines studied, HT-29 proved to be the most susceptible to the treatment with compounds having ROS-generating potency.

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Effect of tamoxifen and fulvestrant long-term treatments on ROS production and (pro/anti)-oxidant enzymes mRNA levels in a MCF-7-derived breast cancer cell line

Cited by 8 publications

References 32 publications

Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers

Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers

Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer

Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character

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