Deciphering the Effect of a Cu(II)-hydrazone Complex on Intracellular Cell Signalling Pathways in a Human Osteosarcoma 2D and 3D Models.

New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children.The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems.

Metallocompounds as anticancer agents against osteosarcoma.

Metallocompounds are a class of anticancer compounds largely used in the treatment of several types of solid tumors, including bone cancer. Osteosarcoma (OS) is a primary malignant bone tumor that frequently affects children, adolescents and young adults. It is a very invasive type of tumor, so ∼40% of patients develop distant metastases, showing elevated mortality rates.

Promising Dual Anticancer and Antimetastatic Action by a Cu(II) Complex Derived from Acylhydrazone on Human Osteosarcoma Models.

Osteosarcoma cancers are becoming more common in children and young adults, and existing treatments have low efficacy and a very high mortality rate, making it pressing to search for new chemotherapies with high efficacy and high selectivity index. Copper complexes have shown promise in the treatment of osteosarcoma. Here, we report the synthesis, characterization, and anticancer activity of [Cu(N-N-Fur)(NO)(HO)] complex where N-N-Fur is (E)-'-(2-hydroxy-3-methoxybenzylidene)furan-2-carbohydrazide.

New copper(II) and oxidovanadium(IV) complexes with a vitamin B Schiff base: mechanism of action and synergy studies on 2D and 3D human osteosarcoma cell models.

We report the synthesis, characterization and anticancer activity of a new Schiff base (HL) derived from the condensation of pyridoxamine with pyridoxal and its novel copper(II) and oxidovanadium(IV) complexes: [Cu(HL)Cl] (1), [Cu(LH)(phen)]Cl (2), [Cu(LH)(amphen)]Cl (3), [VO(HL)Cl] (4), and [VO(LH)(phen)]Cl (5), where phen is 1,10-phenanthroline and amphen is its 5-amino derivative. All compounds were characterized by analytical and spectroscopic techniques, namely FTIR, UV-vis and EPR spectroscopy. Their stability in aqueous media was evaluated, revealing that the presence of the phen co-ligand significantly increases the stability.

5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity.

Invited for this month's cover are the collaborating groups of Esteban Rodríguez-Arce from the University of Chile and María Contel from The City University of New York Brooklyn College. The cover picture shows "Supergold" a very powerful gender neutral warrior with superpowers who fights against cancer! The warrior's golden armor and sword represent the pharmacological power of the gold atom. Engraved on the shield, the gold-thiosemicarbazone molecules are the warrior's coat of arms.

Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models.

Osteosarcoma (OS) is a frequent bone cancer, affecting largely children and young adults. Cisplatin (CDDP) has been efficacious in the treatment of different cancer such us OS but the development of chemoresistance and important side effects leading to therapeutic failure. Novel therapies including copper compounds have shown to be potentially effective as anticancer drugs and one alternative to usually employed platinum compounds.

Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.

New heterometallic binuclear and trinuclear platinum(IV)-gold(I) compounds of the type [Pt(L) Cl (OH){(OOC-4-C H -PPh )AuCl} ] (L=NH , n=2; x=1, 2; L=diaminocyclohexane, DACH, n=1; x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu compound containing the Pt core based on oxaliplatin, to further investigate its cell-death pathway, cell and organelle uptake and anticancer effects against the triple-negative breast cancer (TNBC) MDA-MB-231 cell line.

Anticancer activity of Ni(II) and Zn(II) complexes based on new unsymmetrical salophen-type ligands: synthesis, characterization and single-crystal X-ray diffraction.

The discovery of new coordination compounds with anticancer properties is an active field of research due to the severe side effects of platinum-based compounds currently used in chemotherapy. In the search for new agents for the treatment of cancer, unsymmetrical NO-tetradentate ligand (H2L1 and H2L2) and their Ni(II) and Zn(II) asymmetric complexes (NiII-L1-2 and ZnII-L1-2) have been synthesized and fully characterized. H NMR studies revealed that the ligands and complexes were stable in mixtures of DMSO : DO (9 : 1).

5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity.

This work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5-nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)] or [Au(HTSC) ] , and/or dimeric species. Neutral [{Au(TSC)} ] species were obtained from one of the compounds in dichlomethane/n-hexane solution and characterized by X-ray crystallography revealing a Au-Au bond, and deprotonated thiosemicarbazone (TSC).

Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics.

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments.

Exploring pta Alternatives in the Development of Ruthenium-Arene Anticancer Compounds.

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η--cymene)Ru(pyrithionato)(pta)]PF contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs.

Anticancer and Antioxidant Activity of Water-Soluble Polysaccharides from aff. against Human Osteosarcoma Cells.

Wild mushrooms have gained great importance for being a source of biologically active compounds. In this work, we evaluate the anticancer and antioxidant activity of a water-soluble crude polysaccharide extract isolated from the fruiting bodies of the aff. (GACP).

Active and pH-Sensitive Nanopackaging Based on Polymeric Anthocyanin/Natural or Organo-Modified Montmorillonite Blends: Characterization and Assessment of Cytotoxicity.

Polymeric anthocyanins are biologically active, pH-sensitive natural compounds and pigments with beneficial functional, pharmacological and therapeutic properties for consumer health. More recently, they have been used for the manufacture of active and pH-sensitive ("intelligent") food nanopackaging, due to their bathochromic effect. Nevertheless, in order for polymeric anthocyanins to be included either as a functional food or as a pharmacological additive (medicinal food), they inevitably need to be stabilized, as they are highly susceptible to environmental conditions.

New ternary Fe(III)-8-hydroxyquinoline-reduced Schiff base complexes as selective anticancer drug candidates.

Due to the growing prevalence of cancer diseases, new therapeutic options are urgently needed, and drugs based on metal ions other than platinum are alternatives with exciting possibilities. We report the synthesis, characterization and biological effect of mixed-ligand Fe(III)-aminophenolate complexes derived from salicylaldehyde and L-tryptophan with quinoline derivatives as co-ligands, namely 8-hydroxyquinoline (8HQ), [Fe(L)(8HQ)(HO)] (1) and its 5-cloro derivative (Cl8HQ), [Fe(L)(Cl8HQ)(HO)] (2). The complex bearing the aminophenolate and lacking the quinoline co-ligand, [Fe(L)(Cl)(HO)] (3), was prepared for comparison.

Antiproliferative activity of two copper (II) complexes on colorectal cancer cell models: Impact on ROS production, apoptosis induction and NF-κB inhibition.

The main goal of this work was to screen the antiproliferative activity and mechanism of actions of two copper complexes: [Cu(dmp)(CHCN)] (1) and [Cu(phen)(CHCN)] (2) on 2D and 3D colorectal cancer cells models. Cell viability studies on three colorectal cancer cell lines (HT-29, LS174T, Caco-2) displayed that 1 showed more robust antiproliferative activity than 2 and cisplatin. Intracellular copper content (63.

Focal adhesion kinase inhibitors in the treatment of solid tumors: Preclinical and clinical evidence.

Focal Adhesion Kinase (FAK) is a 125-kDa cytoplasmic protein kinase that is implicated in several cellular functions. This protein is an attractive molecular target for cancer therapy because a wide variety of studies have demonstrated associations between the activation or elevated expression of FAK and tumor progression, invasion, and drug resistance in malignant tumors. Here, we review the strategies used to inhibit FAK activity in solid tumors.

Copper Complexes as Antitumor Agents: and Evidence.

Copper is an essential element for most aerobic organisms, with an important function as a structural and catalytic cofactor, and in consequence, it is implicated in several biological actions. The relevant aspects of chemistry and biochemistry and the importance of copper compounds in medicine give us a comprehensive knowledge of the multifaceted applications of copper in physiology and physiopathology. In this review, we present an outline of the chemistry, and the antitumor properties of copper complexes on breast, colon, and lung cancer cells focus on the role of copper in cancer, the relationship between structure-activity, molecular targets, and the study of the mechanism of action involved in its anticancer activity.

Anticancer Activity and Mechanism of Action Evaluation of an Acylhydrazone Cu(II) Complex toward Breast Cancer Cells, Spheroids, and Mammospheres.

The purpose of this work was to screen the anticancer activity and mechanisms of action of Cu(II)-acylhydrazone complex [Cu(HL)(H O)](NO )⋅H O, (CuHL), to find a potential novel agent for breast chemotherapies. Cytotoxicity studies on MCF7 cells demonstrated that CuHL has stronger anticancer properties than cisplatin over breast cancer cell models. Computational simulations showed that CuHL could interact in the minor groove of the DNA dodecamer, inducing a significant genotoxic effect on both cancer cells from 0.

Synergy of DNA intercalation and catalytic activity of a copper complex towards improved polymerase inhibition and cancer cell cytotoxicity.

Improving the binding of metal complexes to DNA to boost cancer cell cytotoxicity requires fine tuning of their structural and chemical properties. Copper has been used as a metal center in compounds containing intercalating ligands due to its ability to catalytically generate reactive oxygen species (ROS), such as hydroxyl radicals (OH˙). We envision the synergy of DNA binding and ROS generation in proximity to target DNA as a powerful chemotherapy treatment.

Lipid, polymeric, inorganic-based drug delivery applications for platinum-based anticancer drugs.

The three main FDA-approved platinum drugs in chemotherapy such as carboplatin, cisplatin, and oxaliplatin are extensively applied in cancer treatments. Although the clinical applications of platinum-based drugs are extremely effective, their toxicity profile restricts their extensive application. Therefore, recent studies focus on developing new platinum drug formulations, expanding the therapeutic aspect.

Long Non-coding RNAs in Cisplatin Resistance in Osteosarcoma.

Osteosarcoma (OS), the most common primary malignant bone tumor, is a vastly aggressive disease in children and adolescents. Although dramatic progress in therapeutic strategies have achieved over the past several decades, the outcome remains poor for most patients with metastatic or recurrent OS. Nowadays, conventional treatment for OS patients is surgery combined with multidrug chemotherapy including doxorubicin, methotrexate, and cisplatin (CDDP).