Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors

Kousidou, Olga Ch.; Mitropoulou, Theoni N.; Roussidis, Andreas E.; Kletsas, Dimitris; Theocharis, Achilleas D.; Karamanos, Nikos K.

doi:10.3892/ijo.26.4.1101

Cited by 59 publications

(63 citation statements)

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“…The activation of LOX is dependent on copper that is internalized and then transported to trans golgi network by copper transporter ATP7A (Pase et al, 2004), a protein mutated in Menkes disease (Moller et al, 2005). Prion protein has also been reported as a (Johnson, 1991;Kousidou et al, 2004;Shao et al, 2005) and promoter methylation (Costa et al, 2004). As several transcripts coding for junctional proteins are downregulated in invasive cells, we postulate that methylation-specific PCR can be exploited to use these transcripts as biomarkers of tumor cells in general and invasiveness in particular.…”

Section: Discussionmentioning

confidence: 99%

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

et al. 2005

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We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2. The altered transcripts identified by microarray analysis were involved in cell-cell or cell-matrix interaction, Rho signaling, calcium homeostasis and copper-binding/sensitive activities. A set of nine genes that included GPCR11, cadherin 11, annexin A1, vimentin, lactate dehydrogenase B (upregulated in MDA-MB-231) and GREB1, S100A8, amyloid b precursor protein, claudin 3 and cadherin 1 (downregulated in MDA-MB-231) were sufficient to distinguish MDA-MB-231 from MCF7 cells. The downregulation of a set of transcripts for proteins involved in cell-cell interaction indicated these transcripts as potential markers for invasiveness that can be detected by methylation-specific PCR. The proteomic profiles indicated altered abundance of fewer proteins as compared to transcript profiles. Antisense knockdown of selected transcripts led to inhibition of cell proliferation that was accompanied by altered proteomic profiles. The proteomic profiles of antisense transfectants suggest the involvement of peptidyl-prolyl isomerase, Raf kinase inhibitor and 80 kDa protein kinase C substrate in mediating the inhibition of cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

et al. 2005

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“…However, it seemed to have no effect on the activity of MMP-3 ( Figure 4). Possible mechanisms of genistein-mediated inhibition of MDA-MB-231 invasion include down-regulation of the transcription of MMP-2, MMP-9, and MT1-MMP, and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) [39,40] . Furthermore, Magee and coworkers [41] demonstrated that other phytoestrogens, including genistein, inhibited MDA-MB-231 cell invasion without affecting cell viability.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

et al. 2009

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IntroductionMetastatic invasion is the primary cause of patient mortality during breast cancer progression. For a transformed cell to metastasize to a distant site in the body, it must first lose adhesion, penetrate and invade the surrounding extracellular matrix (ECM), enter the vascular system, and adhere to distant organs [1] . The inhibition of invasion of cancer cells has been an important strategy in cancer treatment [2] . A crucial step in the invasive processes is the proteolytic degradation of the ECM and basal membranes [3] . Several studies have shown that among the enzymes responsible for ECM degradation, the matrix metalloproteinases (MMPs) appear to play a critical role [4][5][6] . MMPs are zinc-dependent endopeptidases, which collectively can degrade all constituents of the ECM. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, gelatinases, membrane-type MMPs and other MMPs [7] .Breast cancer is the major cause of malignancy-related deaths of women worldwide. In Thailand, breast cancer is the second most common cancer among women and its incidence is increasing [8] . Cancer invasion and metastasis are leading causes of morbidity and mortality in patients with breast cancer. Several studies have demonstrated that upregulation of MMP-1, -2, -3, -7, -9, -13, and -14 is associated with breast cancer cell invasion [9][10][11] .MMP-3, also designated stromelysin 1, is a member of the matrixin family, which plays a pivotal role in the degradation and remodeling of the ECM. MMP-3 degrades several components of the ECM, such as fi bronectin, laminin, collagen type IV [12][13][14] and proteoglycans, and is thought to play an important role in rheumatoid arthritis, osteoarthritis [15,16] , tumor cell invasion and metastasis [17] . Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, fl avonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their ability to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of fl avonoids on MDA-MB-231 cell invasion. Methods: The toxic concentration range of fl avonoids was evaluated using the MTT assay. The ability of MDA-MB-231 cells to invade was evaluated using a modifi ed Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confi rmed by ELISA. Results: Some putative fl avonoids, ie, quercetin and kaempferol (fl avonols), signifi cantly inhibited the in vitro invasion of MDA-MB-231 cells in a concentration-dependent manner, with IC 50 values of 27 and 30 μmol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC 50 values in the range of 30 μmol/L and 45 μmol/L, respectively. None of the fl avonoids had a signif...

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“…Another agent is Genistein a soy isoflavonoid similar to estradiol which interferes with the expression of several MMPs and TIMPs (Kousidou et al, 2006).…”

Section: Natural Mmp Inhibitorsmentioning

confidence: 99%

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Yadav¹,

Puri²,

Rastogi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

187

131

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Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

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Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors

Cited by 59 publications

References 0 publications

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

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