Altered DNA Binding and Amplification of Human Breast Cancer Suppressor Gene BRCA1 Induced by a Novel Antitumor Compound, [Ru(η6-p-phenylethacrynate)Cl2(pta)]

Chakree, Korawan; Ovatlarnporn, Chitchamai; Dyson, Paul J.; Ratanaphan, Adisorn

doi:10.3390/ijms131013183

Cited by 21 publications

(14 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…About 10 6 cells were incubated with various concentrations of 1 or 2 at 37°C for 48 h in 5% CO 2 . Genomic DNA of the ruthenium-treated or untreated (control) cells was isolated, and the 3426-bp fragment of the BRCA1 exon 11 of the cells was then amplified by PCR, electrophoresed on 1% agarose gel, stained with ethidium bromide and then visualized under UV light [ 20 ]. The quantitative PCR (QPCR) method was used to assess the polymerase inhibiting effect of DNA ruthenation.…”

Section: Methodsmentioning

confidence: 99%

“…The quantitative PCR (QPCR) method was used to assess the polymerase inhibiting effect of DNA ruthenation. The amplification products were quantified using a Bio-Rad Molecular Imager, and the amount of DNA amplification (%) was plotted as a function of the concentration [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Several ruthenium compounds have exhibited high cytotoxicity towards cancer cells and for inducing apoptosis [ 15 - 17 ]. In addition, extensive investigations of ruthenium-based compounds has mainly focused on the characterization of ruthenium-DNA adducts [ 12 , 18 - 20 ] and has paid less attention to other potential cellular targets. For ruthenium-based drug candidates, their precise mechanisms of action as anticancer activities remain comparatively unexplored.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundTriple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Breast cancers with a BRCA1 mutation are also frequently triple-negative. Currently, there is a lack of effective therapies and known specific molecular targets for this aggressive breast cancer subtype. To address this concern, we have explored the cellular responses of BRCA1-defective and triple-negative breast cancer cells, and in vitro BRCA1 interactions induced by the ruthenium(II) complexes containing the bidentate ligand, 5-chloro-2-(phenylazo)pyridine.MethodsTriple-negative MDA-MB-231, BRCA1-defective HCC1937 and BRCA1-competent MCF-7 breast cancer cell lines were treated with ruthenium(II) complexes. The cytoxoxicity of ruthenium-induced breast cancer cells was evaluated by a real time cellular analyzer (RTCA). Cellular uptake of ruthenium complexes was determined by ICP-MS. Cell cycle progression and apoptosis were assessed using propidium iodide and Annexin V flow cytometry. The N-terminal BRCA1 RING protein was used for conformational and functional studies using circular dichroism and in vitro ubiquitination.ResultsHCC1937 cells were significantly more sensitive to the ruthenium complexes than the MDA-MB-231 and MCF-7 cells. Treatment demonstrated a higher degree of cytotoxicity than cisplatin against all three cell lines. Most ruthenium atoms were retained in the nuclear compartment, particularly in HCC1937 cells, after 24 h of incubation, and produced a significant block at the G2/M phase. An increased induction of apoptotic cells as well as an upregulation of p53 mRNA was observed in all tested breast cancer cells. It was of interest that BRCA1 mRNA and replication of BRCA1-defective cells were downregulated. Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were observed, causing inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase activity.ConclusionsThis study has revealed the ability of ruthenium complexes to inhibit cell proliferation, induce cell cycle progression and apoptosis. Ruthenium treatment upregulated the marker genes involved in apoptosis and cell cycle progression while it downregulated BRCA1 mRNA and replication of HCC1937 cells. Our results could provide an alternative approach to finding effective therapeutic ruthenium-based agents with promising anticancer activity, and demonstrated that the BRCA1 RING domain protein was a promising therapeutic target for breast cancers.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because STAT3 is commonly overexpressed in AML, flavopiridol remains of particular interest against this hematological disorder [ 290 ]. Some metallo-intercalators associating ruthenium or platinum atom to stabilize rings in a planar configuration were also evidenced as inhibitors of protein/DNA binding like for example, [Ru(phen) 2 (dppz)] 2+ against the interaction of PUrine-rich box-1 (PU.1)/SFFV Proviral Integration Site-1 (SPI1), an ETS-family member transcription factor, to its minimal cognate ETS-family-core binding site 5′-GGAA/T-3′ [ 291 ], or ethaRAPTA against the DNA repair protein BRCA1 also associated with transcription control [ 292 ].…”

Section: Targeting Transcription Factor At the Protein/dna Interacmentioning

confidence: 99%

Targeting Transcription Factors for Cancer Treatment

et al. 2018

View full text Add to dashboard Cite

Transcription factors are involved in a large number of human diseases such as cancers for which they account for about 20% of all oncogenes identified so far. For long time, with the exception of ligand-inducible nuclear receptors, transcription factors were considered as “undruggable” targets. Advances knowledge of these transcription factors, in terms of structure, function (expression, degradation, interaction with co-factors and other proteins) and the dynamics of their mode of binding to DNA has changed this postulate and paved the way for new therapies targeted against transcription factors. Here, we discuss various ways to target transcription factors in cancer models: by modulating their expression or degradation, by blocking protein/protein interactions, by targeting the transcription factor itself to prevent its DNA binding either through a binding pocket or at the DNA-interacting site, some of these inhibitors being currently used or evaluated for cancer treatment. Such different targeting of transcription factors by small molecules is facilitated by modern chemistry developing a wide variety of original molecules designed to specifically abort transcription factor and by an increased knowledge of their pathological implication through the use of new technologies in order to make it possible to improve therapeutic control of transcription factor oncogenic functions.

show abstract

“…This leads to the emergence of cancer. BRCA1 has been confirmed to be related to COAD [23]. BRCA2 is a tumor suppressor gene, which is mainly involved in the repair of DNA damage and regulation of transcription.…”

Section: Resultsmentioning

confidence: 99%

Co-differential Gene Selection and Clustering Based on Graph Regularized Multi-View NMF in Cancer Genomic Data

Gao

Liu

et al. 2018

Genes

View full text Add to dashboard Cite

Cancer genomic data contain views from different sources that provide complementary information about genetic activity. This provides a new way for cancer research. Feature selection and multi-view clustering are hot topics in bioinformatics, and they can make full use of complementary information to improve the effect. In this paper, a novel integrated model called Multi-view Non-negative Matrix Factorization (MvNMF) is proposed for the selection of common differential genes (co-differential genes) and multi-view clustering. In order to encode the geometric information in the multi-view genomic data, graph regularized MvNMF (GMvNMF) is further proposed by applying the graph regularization constraint in the objective function. GMvNMF can not only obtain the potential shared feature structure and shared cluster group structure, but also capture the manifold structure of multi-view data. The validity of the proposed GMvNMF method was tested in four multi-view genomic data. Experimental results showed that the GMvNMF method has better performance than other representative methods.

show abstract

Altered DNA Binding and Amplification of Human Breast Cancer Suppressor Gene BRCA1 Induced by a Novel Antitumor Compound, [Ru(η6-p-phenylethacrynate)Cl2(pta)]

Cited by 21 publications

References 55 publications

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

Targeting Transcription Factors for Cancer Treatment

Co-differential Gene Selection and Clustering Based on Graph Regularized Multi-View NMF in Cancer Genomic Data

Contact Info

Product

Resources

About