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Breast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their [EC.sub.50] concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of [omega]6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of [omega]3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of [omega]6 linoleic, arachidonic acids, and [omega]3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin. Key words: somatostatin, curcumin, quercetin, breast cancer, cell signaling, membrane fatty acid profile. Le cancer du sein est une maladie frequente chez les femmes a l'echelle mondiale et son traitement efficace est considere comme etant un immense probleme clinique, meme en presence de plusieurs options therapeutiques. Il existe une grande quantite de donnees publiees decrivant les polyphenols comme etant des agents phytopharmaceutiques anticancereux. Parmi les polyphenols, on a rapporte que la quercetine et la curcumine sont potentiellement fort utiles contre le cancer du sein. Cependant, jusqu'a maintenant, aucune etude exhaustive n'a tente de montrer les effets anticancerigenes de la curcumine, de la quercetine et de leur association avec la somatostatine sur le profil des acides gras membranaires des cellules de cancer du sein. A l'aide de cellules de cancer du sein MCF-7 et MDA-MB231 incubees avec de la curcumine et de la quercetine pendant 24 h, en absence ou en presence de somatostatine et a leur concentration efficace mediane, nous avons evalue la lipidomique fonctionnelle basee sur les acides gras membranaires ainsi que suivi les voies de signalisation des recepteurs du facteur de croissance epidermique (EGF pour << epidermal growth factor >>) et de la MAP kinase. Les deux lignees cellulaires ont donne differentes reorganisations des acides gras libres. Dans les cellules MCF-7, nous avons observe les modifications suivantes : hausse de l'acide linoleique [omega]6 avec l'association somatostatine + quercetine et la quercetine, et abaissement des acides gras [omega]3 plus marque dans les cellules incubees avec l'association somatostatine + quercetine qu'avec la somatostatine, ainsi qu'une augmentation notable plus importante des taux d'acides gras mono-insatures, d'acide arachidonique mono-trans et d'acide docosapentaenoique pour les cellules incubees avec l'association somatostatine + quercetine que chez les cellules temoins. Pour les cellules MDA-MB231, l'incubation avec de la curcumine, de la quercetine et l'association somatostatine + quercetine a entraine le plus important remodelage membranaire avec une hausse de l'acide stearique, un abaissement des acides gras linoleique [omega]6, arachidonique et [omega]3 (acides docosapentaenoique et docosahexaenoique). Nous avons observe des modifications distinctes des voies de signalisation pour ces lignees cellulaires. Pour les cellules MCF-7, l'incubation avec de la somatostatine ou de la quercetine separement ou en association entrainait une inhibition marquee de la voie de signalisation des recepteurs de l'EGF, et l'incubation avec de la curcumine entrainait une inhibition de la voie de signalisation de la MAP kinase. L'incubation des cellules MDA-MB231 avec de la curcumine a entraine une diminution des taux d'AKTl et de p-AKT1 (Thr308). L'incubation avec de la curcumine et de la quercetine entrainait une diminution des taux des recepteurs de l'EGF. Nos resultats ont montre que des traitements cytostatiques et antioxydants peuvent etre associes pour produire des changements dans les acides gras membranaires, y compris une isomerisation lipidique en tant que processus specifique entraine par les radicaux libres, ainsi que pour influencer les voies de signalisation. Cette etude visait a ajouter aux connaissances publiees quant a l'utilisation de ces antioxydants dans le traitement du cancer du sein, en vue d'en clarifier les effets et les modes d'action en association avec la somatostatine. [Traduit par la Redaction] Mots-cles: somatostatine, curcumine, quercetine, cancer du sein, signalisation cellulaire, profil des acides gras membranaires., Introduction Cancer is a deadly global disease and a critical barrier in the cumulative life span of the affected population (Bray et al. 2018). On the basis of the recorded [...]

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi=9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence. [ABSTRACT FROM AUTHOR]

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi=9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence. [ABSTRACT FROM AUTHOR]

This article, published in Angewandte Chemie, discusses various research findings in the field of chemistry. One study focuses on the binding of a ruthenium diimine complex to DNA, revealing its sequence and enantiospecificity. Another study presents a strategy for site-selectivity in complex molecules based on metal ion-induced large fragment deactivation. Additionally, researchers develop a universal strategy for constructing catalysts with high performance in CO2 hydrogenation to methanol. Lastly, a biosensing system based on supersandwich DNA probes and solid-state nanochannels is developed. The article provides valuable insights for researchers in the field of chemistry. [Extracted from the article]

This article, published in Angewandte Chemie International Edition, discusses various research articles in the field of chemistry. One research article by Christine Cardin, Andrew Kellett, and others explores the binding of a ruthenium diimine complex to DNA, specifically focusing on its sequence and enantiospecificity. Another research article by Travis Dudding, Thomas Lectka, and colleagues presents a strategy for site-selectivity in complex molecules based on metal ion-induced large fragment deactivation. Xiaohao Liu and his team develop a universal strategy for constructing In2O3-supported diatomic Ir-Pd sites for CO2 hydrogenation to methanol. Lastly, Yu Huang, Fan Xia, and their team develop a multi-function biosensing system based on supersandwich DNA probes and solid-state nanochannels. [Extracted from the article]

We report a series of copper(II) artificial metallo‐nucleases (AMNs) and demonstrate their DNA damaging properties and in‐vitro cytotoxicity against human‐derived pancreatic cancer cells. The compounds combine a tris‐chelating polypyridyl ligand, di‐(2‐pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu‐DPA‐N,N' (where N,N'=1,10‐phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X‐ray crystallography and continuous‐wave EPR (cw‐EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron‐nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (Kapp) rising from 105 to 107 m−1 with increasing extent of planar phenanthrene. Cu‐DPA‐DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G‐C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu‐DPA‐DPPZ, display promising anticancer activity against human pancreatic tumour cells with in‐vitro results surpassing the clinical platinum(II) drug oxaliplatin. [ABSTRACT FROM AUTHOR]

The building of robust and versatile inorganic scaffolds with artificial metallo‐nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and metallodrug research fields. Here, a new type of AMN combining a tris‐(2‐pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N′‐phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10‐phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)(N,N′)]2+ (where N,N′ is 2,2‐bipyridine (Bipy), Phen, 1,10‐phenanthroline‐5,6‐dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X‐ray crystallography. Solution stabilities were studied by continuous‐wave EPR (cw‐EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron–nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin‐trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman‐ and Fenton‐type reagents. A new type of artificial metallo‐nuclease (AMN) combining the tris‐(2‐pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N′‐phenanthrene chemical nuclease core is reported. Five compounds of formula [Cu(TPMA)(N,N′)](ClO4)2 were structurally determined by X‐ray crystallography and their solution properties characterized by EPR spectroscopic techniques. DNA intercalation, oxidative damage, and repair enzyme recognition demonstrated distinctive AMN activity and DNA oxidation compared to classical Sigman‐ and Fenton‐type reagents. [ABSTRACT FROM AUTHOR]

Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress--with an excess of radical and oxidative processes--cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects. [ABSTRACT FROM AUTHOR]

Cover Feature: Polypyridyl-Based Copper Phenanthrene Complexes: Combining Stability with Enhanced DNA Recognition (Chem. Eur. J. 3/2021) Keywords: copper; DNA damage; DNA repair; electrochemistry; EPR spectroscopy EN copper DNA damage DNA repair electrochemistry EPR spectroscopy 828 828 1 01/18/21 20210113 NES 210113 B A new class of DNA intercalating metallodrug is reported b . Copper, DNA damage, DNA repair, electrochemistry, EPR spectroscopy. [Extracted from the article]

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi=9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence. [ABSTRACT FROM AUTHOR]

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi=9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence. [ABSTRACT FROM AUTHOR]

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ-[Ru(phen) 2 phi] 2+ , where phi=9,10-phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG) 2 . The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ-enantiomer and show a high affinity for TA/TA steps and, more generally, TA-rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (K app ) rising from 10 5 to 10 7  m -1 with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine-cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin., (© 2020 Wiley-VCH GmbH.)

The building of robust and versatile inorganic scaffolds with artificial metallo-nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and metallodrug research fields. Here, a new type of AMN combining a tris-(2-pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N'-phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10-phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)(N,N')] 2+ (where N,N' is 2,2-bipyridine (Bipy), Phen, 1,10-phenanthroline-5,6-dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X-ray crystallography. Solution stabilities were studied by continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron-nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin-trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman- and Fenton-type reagents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of copper complexes for redox and oxidative-based mechanisms in therapeutic strategies is an important field of multidisciplinary research. Here, a novel Cu(II) complex [Cu(TPMA)(Phen)](ClO 4 ) 2 (Cu-TPMA-Phen, where TPMA = tris-(2-pyridylmethyl)amine and Phen = 1,10-phenanthroline) was studied using both the free and encapsulated forms. A hollow pH-sensitive drug-delivery system was synthesized, characterized, and used to encapsulate and release the copper complex, thus allowing for the comparison with the free drug. The human neuroblastoma-derived cell line NB100 was treated with 5 μM Cu-PMA-Phen for 24 h, pointing to the consequences on mono- and polyunsaturated fatty acids (MUFA and PUFA) present in the membrane lipidome, coupled with cell viability and death pathways (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium viability assay, flow cytometry, microscopy, caspase activation). In parallel, the Cu-TPMA-Phen reactivity with the fatty acid moieties of phospholipids was studied using the liposome model to work in a biomimetic environment. The main results concerned: (i) the membrane lipidome in treated cells, involving remodeling with a specific increase of saturated fatty acids (SFAs) and a decrease of MUFA, but not PUFA; (ii) cytotoxic events and lipidome changes did not occur for the encapsulated Cu-TPMA-Phen, showing the influence of such nanocarriers on drug activity; and (iii) the liposome behavior confirmed that MUFA and PUFA fatty acid moieties in membranes are not affected by oxidative and isomerization reactions, proving the different reactivities of thiyl radicals generated from amphiphilic and hydrophilic thiols and Cu-TPMA-Phen. This study gives preliminary but important elements of copper(II) complex reactivity in cellular and biomimetic models, pointing mainly to the effects on membrane reactivity and remodeling based on the balance between SFA and MUFA in cell membranes that are subjects of strong interest for chemotherapeutic activities as well as connected to nutritional strategies., Competing Interests: The authors declare no competing financial interest.