Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells

Vasaturo, Fortunata; Malacrino, Carolina; Sallusti, E; Coppotelli, Giuseppe; Birarelli, P; Giuffrida, A. M.; Albonici, Loredana; Simonelli, Lucilla; Modesti, Andrea; Modesti, M; Scarpa, Susanna

doi:10.3892/or.13.4.745

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…This can be explained by the fact that Staurosporine is a competitive inhibitor of protein kinases that binds in the binding pockets of target kinases by competing with ATP molecule [ 48 ]. Similar findings have been reported by various studies regarding the ability of Staurosporine as an effective antitumor molecule with potential activity seen in various cancer cell lines (breast, colon, cervical and oral) [ 49 , 50 , 51 ]. In vitro analysis has revealed that Staurosporine induces apoptosis in many cell lines [ 52 ].…”

Section: Discussionsupporting

confidence: 89%

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

et al. 2023

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In glucose metabolism, the pentose phosphate pathway (PPP) is the major metabolic pathway that plays a crucial role in cancer growth and metastasis. Although it has been pointed out that blockade of the PPP is a promising approach against cancer, in the clinical setting, effective anti-PPP agents are still not available. Dysfunction of the G6PD enzyme in this pathway leads to cancer development as this enzyme possesses oncogenic activity. In the present study, an attempt was made to identify bioactive compounds that can be developed as potential G6PD inhibitors. In the present study, 11 natural compounds and a controlled drug were taken. The physicochemical and toxicity properties of the compounds were determined via ADMET and ProTox-II analysis. In the present study, the findings of docking studies revealed that staurosporine was the most effective compound with the highest binding energy of −9.2 kcal/mol when docked against G6PD. Homology modeling revealed that 97.56% of the residues were occupied in the Ramachandran-favored region. The modeled protein gave a quality Z-score of −10.13 by ProSA tool. iMODS server provided significant insights into the mobility, stability and flexibility of the G6PD protein that described the collective functional protein motion. In the present study, the physical and functional interactions between proteins were determined by STRING. CASTp server determined the topological and geometric properties of the G6PD protein. The findings of the present study revealed that staurosporine could be developed as a potential G6PD inhibitor; however, further in vivo and in vitro studies are needed for further validation of these results.

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Section: Discussionsupporting

confidence: 89%

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

et al. 2023

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“…For example, interaction of integrin alpha 2-beta 1 receptor complex with collagen type II and laminin coated surfaces results in ligand-induced Smad2 activation [44]. Modification of ECM components modulates the staurosporine-induced apoptotic process of breast cancer cells through modulation in Raf/MAP kinase pathway activity [45]. ECM proteins also influence proliferation and cytokine expression in various human breast cancer cell lines [46].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Alkaline pH Leads to Increased Metastatic Potential of Estrogen Receptor Silenced Endocrine Resistant Breast Cancer Cells

et al. 2013

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IntroductionEndocrine resistance in breast cancer is associated with enhanced metastatic potential and poor clinical outcome, presenting a significant therapeutic challenge. We have established several endocrine insensitive breast cancer lines by shRNA induced depletion of estrogen receptor (ER) by transfection of MCF-7 cells which all exhibit enhanced expression profile of mesenchymal markers with reduction of epithelial markers, indicating an epithelial to mesenchymal transition. In this study we describe their behaviour in response to change in extracellular pH, an important factor controlling cell motility and metastasis.MethodsMorphological changes associated with cell exposure to extracellular alkaline pH were assessed by live cell microscopy and the effect of various ion pumps on this behavior was investigated by pretreatment with chemical inhibitors. The activity and expression profile of key signaling molecules was assessed by western blotting. Cell motility and invasion were examined by scratch and under-agarose assays respectively. Total matrix metalloproteinase (MMP) activity and specifically of MMP2/9 was assessed in conditioned medium in response to brief alkaline pH exposure.ResultsExposure of ER –ve but not ER +ve breast cancer cells to extracellular alkaline pH resulted in cell shrinkage and spherical appearance (termed contractolation); this was reversed by returning the pH back to 7.4. Contractolation was blocked by targeting the Na+/K+ and Na+/H+ pumps with specific chemical inhibitors. The activity and expression profile of key signaling molecules critical for cell adhesion were modulated by the exposure to alkaline pH. Brief exposure to alkaline pH enhanced MMP2/9 activity and the invasive potential of ER –ve cells in response to serum components and epithelial growth factor stimulation without affecting unhindered motility.ConclusionsEndocrine resistant breast cancer cells behave very differently to estrogen responsive cells in alkaline pH, with enhanced invasive potential; these studies emphasise the crucial influence of extracellular pH and caution against indiscriminate application of alkalinising drug therapy.

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“…This selected a number of clones encoding 37LRP, as well as Hsp60 (heat-shock protein 60) molecular chaperones. The surface expression of functional 37LRP/67LR appears to be a prerequisite for both binding and internalization of PrP, as 37LRP mutants lacking the putative transmembrane domain (residues [86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101] were not retained at the membrane, but mutated 37LRP was isolated from the extracellular space. Tissues with high levels of PrP sc (the modified pathogenic form of PrP) accumulation displayed correspondingly high levels of 37LRP, in particular the brain and pancreatic tissue [128].…”

Section: Prp Interactionsmentioning

confidence: 99%

The 67 kDa laminin receptor: structure, function and role in disease

et al. 2008

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The 67LR (67 kDa laminin receptor) is a cell-surface receptor with high affinity for its primary ligand. Its role as a laminin receptor makes it an important molecule both in cell adhesion to the basement membrane and in signalling transduction following this binding event. The protein also plays critical roles in the metastasis of tumour cells. Isolation of the protein from either normal or cancerous cells results in a product with an approx. molecular mass of 67 kDa. This protein is believed to be derived from a smaller precursor, the 37LRP (37 kDa laminin receptor precursor). However, the precise mechanism by which cytoplasmic 37LRP becomes cell-membrane-embedded 67LR is unclear. The process may involve post-translational fatty acylation of the protein combined with either homo- or hetero-dimerization, possibly with a galectin-3-epitope-containing partner. Furthermore, it has become clear that acting as a receptor for laminin is not the only function of this protein. 67LR also acts as a receptor for viruses, such as Sindbis virus and dengue virus, and is involved with internalization of the prion protein. Interestingly, unmodified 37LRP is a ribosomal component and homologues of this protein are found in all five kingdoms. In addition, it appears to be strongly associated with histones in the eukaryotic cell nucleus, although the precise role of these interactions is not clear. Here we review the current understanding of the structure and function of this molecule, as well as highlighting areas requiring further research.

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Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells

Cited by 6 publications

References 24 publications

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

Computational Approaches for Identification of Potential Plant Bioactives as Novel G6PD Inhibitors Using Advanced Tools and Databases

Extracellular Alkaline pH Leads to Increased Metastatic Potential of Estrogen Receptor Silenced Endocrine Resistant Breast Cancer Cells

The 67 kDa laminin receptor: structure, function and role in disease

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