Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Zając, Magdalena; Moneo, Maria Victoria; Carnero, Amancio; Benítez, Javier; Martı́nez-Delgado, Beatriz

doi:10.1158/1535-7163.mct-08-0327

Cited by 23 publications

(21 citation statements)

References 29 publications

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“…The two BLBC cell lines used in our experiments both express wild-type BRCA1 protein and are proficient in radiation-induced DNA DSB repair [44, 45]. KU70/80 and DNA-PKcs are of vital importance in NHEJ, the predominant pathway for the repair of radiation-induced DSBs in human cells [45].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation

Zou

Xia

et al. 2017

Cell Physiol Biochem

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Background/Aims: Triple-negative breast cancer (TNBC) is a high-risk breast cancer phenotype without specific targeted therapy options and is significantly associated with increased local recurrence in patients treated with radiotherapy. CAVEOLIN-1 (CAV-1)-mediated epidermal growth factor receptor (EGFR) nuclear translocation following irradiation promotes DNA repair and thus induces radiation resistance. In this study, we aimed to determine whether knockdown of CAV-1 enhances the radiosensitivity of basal-like TNBC cell lines and to explore the possible mechanisms. Methods: Western blotting was used to compare protein expression in a panel of breast cancer cell lines. Nuclear accumulation of EGFR as well as DNA repair and damage at multiple time points following irradiation with or without CAV-1 siRNA pretreatment were investigated using western blotting and confocal microscopy. The radiosensitizing effect of CAV-1 siRNA was evaluated using a clonogenic assay. Flowcytometry was performed to analyse cell apoptosis and cell cycle alteration. Results: We found that CAV-1 is over-expressed in basal-like TNBC cell lines and barely expressed in HER-2-positive cells; additionally, we observed that HER-2-positive cell lines are more sensitive to irradiation than basal-like TNBC cells. Our findings revealed that radiation-induced EGFR nuclear translocation was impaired by knockdown of CAV-1. In parallel, radiation-induced elevation of DNA repair proteins was also hampered by pretreatment with CAV-1 siRNA before irradiation. Silencing of CAV-1 also promoted DNA damage 24 h after irradiation. Colony formation assays verified that cells could be radiosensitized after knockdown of CAV-1. Furthermore, G₂/M cell cycle arrest and apoptosis enhancement may also contribute to the radiosensitizing effect of CAV-1 siRNA. Conclusion: Our results support the hypothesis that CAV-1 knockdown by siRNA causes increased radiosensitivity in basal-like TNBC cells. The mechanisms associated with this effect are reduced DNA repair through delayed CAV-1-associated EGFR nuclear accumulation and induction of G₂/M arrest and apoptosis through the combined effects of CAV-1 siRNA and radiation.

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Section: Discussionmentioning

confidence: 99%

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation

Zou

Xia

et al. 2017

Cell Physiol Biochem

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“…However, the effects of the Hsp90 inhibition are very complex and depend on the biochemical features and molecular background of treated cells [42]. The reported cell cycle effects are mostly G1 and G2/M arrest [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

The alterations in SATB1 and nuclear F-actin expression affect apoptotic response of the MCF-7 cells to geldanamycin

Grzanka

Izdebska

Klimaszewska‐Wiśniewska

et al. 2015

Folia Histochem Cytobiol.

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Introduction. The function and localization of actin in the nucleus have not yet been fully described. However, actin seems to be a key protein in nuclear processes interacting with chromatin and matrix proteins. The aim of the study was to evaluate the effect of controlled expression of nuclear pool of F-actin and special AT-rich sequence-binding protein 1 (SATB1) on the in vitro induction of active cell death by geldanamycin (GA). Material and methods. The expression of SATB1 was regulated by the transfection of non-aggressive breast cancer MCF-7 cells with siRNA against SATB1 or expression plasmid with cloned cDNA of SATB1. The altered expression of cofilin-1 in these cells was used to regulate the nuclear expression and localization of F-actin. The effect of GA was analyzed in the context of cell death induction and cell cycle alterations. Results. Our studies revealed that the targeted regulation of SATB1 and cofilin-1 expression changed the apoptotic response of the MCF-7 cells to GA. The overexpression of these proteins potentiated GA-induced arrest of the cells in the G1 phase of cell cycle and increased the population of the hypodiploid cells. Conclusion. The alterations in the nuclear expression of SATB1 and F-actin in MCF-7 cells may affect their active cell death in response to GA.

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“…Therefore, our data are in agreement with previous reports demonstrating that the induction of cell cycle arrest of breast cancer cells is associated with increased expression of cyclin G1, CHEK1, CDKN1C (p57, Kip2), GADD45A, and E2F2. [34][35][36][37][38] In addition, cycle arrest of MDA-MB-231 cells can be mediated by the inhibition of cyclin A1 and CDK6. 39,40 In this study, we found that BD suppresses invasive behavior of MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Proliferation and Invasive Behavior of Human Metastatic Breast Cancer Cells by Dietary Supplement BreastDefend

et al. 2010

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Aim: The study was to evaluate the effect of the dietary supplement BreastDefend (BD) on the proliferation and invasive behavior of highly metastatic human breast cancer cells in vitro. Methods: Cell proliferation and cytotoxicity of BD was evaluated in MDA-MB-231 cells treated with BD (0-40 μg/mL) by MTT assay and trypan blue staining, respectively. Expression of cell cycle regulatory genes were determined by DNA-microarray analysis. Effect of BD on invasiveness was assessed by cellular adhesion, migration, and invasion assays. Results: BD treatment of cells MDA-MB-231 resulted in the cytostatic inhibition of cell proliferation with IC 50 22.2, 19.1, and 17.5 μg/mL for 24, 48, and 72 hours, respectively. The inhibition of proliferation was mediated by the upregulation expression of CCNG1, CHEK1, CDKN1C, GADD45A, and E2F2, whereas BD downregulated expression of CCNA1 and CDK6 genes. The induction of expression of GADD45A and inhibition of expression of cyclin A1 (gene CCNA1) by BD was also confirmed on the protein level. BD treatment suppressed the invasive behavior of MDA-MB-231 cells by the inhibition of cellular adhesion, migration, and invasion. This inhibition of invasiveness was mediated by the suppression of secretion of urokinase plasminogen activator (uPA), and by the downregulation of expression of CXCR4 in breast cancer cells treated with BD. Conclusion: BD inhibits proliferation and invasive behavior of the highly metastatic human breast cancer cells in vitro. BD may have a therapeutic potential for prevention or treatment of highly metastatic breast cancers.

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Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Cited by 23 publications

References 29 publications

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation

The alterations in SATB1 and nuclear F-actin expression affect apoptotic response of the MCF-7 cells to geldanamycin

Suppression of Proliferation and Invasive Behavior of Human Metastatic Breast Cancer Cells by Dietary Supplement BreastDefend

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