On the cytotoxic activity of Pd(II) complexes of N,N-disubstituted-N′-acyl thioureas

The rational design of anticancer drugs is one of the most promising strategies for increasing their cytotoxicity and for minimizing their toxicity. Manipulation of the structure of ligands or of complexes represents a strategy for which is possible to modify the potential mechanismof their action against the cancer cells. Here we present the cytotoxicity of some new palladium complexes and our intention is to show the importance of noncoordinated atoms of the ligands in the cytotoxicity of the complexes. New complexes of palladium (II), with general formulae [Pd(PPh3)2(L)]PF6 or [PdCl(PPh3)(L)], where L = N,N-disubstituted-N′-acyl thioureas, were synthesized and characterized by elemental analysis, molar conductivity, melting points, IR, NMR(1H, 13C and 31P{1H}) spectroscopy. The spectroscopic data are consistent with the complexes containing an O, S chelated ligand. The structures of complexes with N,N-dimethyl-N′-benzoylthiourea, N,N-diphenyl-N′-benzoylthiourea, N,N-diethyl-N′-furoylthiourea, and N,N-diphenyl-N′-furoylthiourea were determined by X-ray crystallography, confirming the coordination of the ligands with the metal through sulfur and oxygen atoms, forming distorted square-planar structures. The N,N-disubstituted-N′-acyl thioureas and their complexes were screened with respect to their antitumor cytotoxicity against DU-145 (human prostate cancer cells), MDA-MB-231 (human breast cancer cells) and their toxicity against the L929 cell line (health cell line from mouse).CAPESCNPqFAPES

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients

[10]-Gingerol Reverts Malignant Phenotype of Breast Cancer Cells in 3D Culture.

Breast cancer is a complex and multifactorial disease. Tumors have a heterogeneous microenvironment, which have multiple interactions with other cell types, greatly influencing the behavior of tumor cells and response to therapy. The 3D culture mimics the microenvironment better found in vivo and is more appropriated than the traditional 2D culture made from plastic to test the cellular response to drugs. To investigate the effects of [10]-gingerol on breast tumor cells, we used physiologically relevant three-dimensional (3D) cultures of malignant and non-malignant human breast cells grown in laminin-rich extracellular matrix gels (lr-ECM). Our results showed selective cytotoxicity of [10]-gingerol against the malignant T4-2 breast cancer cell line compared to non-malignant S1 cells. The compound reverted the malignant phenotype of the cancer cells, downregulating the expression of epidermal growth factor receptor (EGFR) and β1-integrin. Moreover, [10]-gingerol induced apoptosis in this cell line. These results suggest that [10]-gingerol may be an effective compound to use as adjuvant therapy in breast cancer treatment. J. Cell. Biochem. 118: 2693-2699, 2017. © 2017 Wiley Periodicals, Inc

[10]-Gingerol Reverts Malignant Phenotype of Breast Cancer Cells in 3D Culture.

Breast cancer is a complex and multifactorial disease. Tumors have a heterogeneous microenvironment, which have multiple interactions with other cell types, greatly influencing the behavior of tumor cells and response to therapy. The 3D culture mimics the microenvironment better found in vivo and is more appropriated than the traditional 2D culture made from plastic to test the cellular response to drugs. To investigate the effects of [10]-gingerol on breast tumor cells, we used physiologically relevant three-dimensional (3D) cultures of malignant and non-malignant human breast cells grown in laminin-rich extracellular matrix gels (lr-ECM). Our results showed selective cytotoxicity of [10]-gingerol against the malignant T4-2 breast cancer cell line compared to non-malignant S1 cells. The compound reverted the malignant phenotype of the cancer cells, downregulating the expression of epidermal growth factor receptor (EGFR) and β1-integrin. Moreover, [10]-gingerol induced apoptosis in this cell line. These results suggest that [10]-gingerol may be an effective compound to use as adjuvant therapy in breast cancer treatment. J. Cell. Biochem. 118: 2693-2699, 2017. © 2017 Wiley Periodicals, Inc

Fully disposable microfluidic electrochemical device for detection of estrogen receptor alpha breast cancer biomarker

A novel fully disposable microfluidic electrochemical array device (?FED) was developed and successfully applied for detection of the biomarker estrogen receptor alpha (ER?). The ?FED was constructed using low-cost materials and an inexpensive home cutter printer enabled the manufacture of dozens of ?FEDs in less than 2h, at a cost of less than US$ 0.20 in material per device. The ?FED incorporates counter and reference electrodes and eight carbon-based working electrodes, which were modified with DNA sequences known as estrogen response elements (DNA-ERE), where ER? binds specifically. Paramagnetic particles heavily decorated with anti-ER? antibody and horseradish peroxidase (MP-Ab-HRP) were used to efficiently capture ER? from the sample solution. The ER?-MP-Ab-HRP bioconjugate formed was injected into the ?FED and incubated with the DNA-ERE-modified electrodes, followed by amperometric detection with application of -0.2V vs. Ag|AgCl while a mixture of H2O2 and hydroquinone was injected into the microfluidic device. An ultralow limit of detection of 10.0 fg mL(-1) was obtained with the proposed method. The performance of the assay, in terms of sensitivity and reproducibility, was studied using undiluted calf serum, and excellent recoveries in the range of 94.7-108% were achieved for the detection of ER? in MCF-7 cell lysate. The ?FED system can be easily constructed and applied for multiplex biomarker detection, making the device an excellent cost-effective alternative for cancer diagnosis, especially in developing countries

Evaluation of the cytotoxicity on breast cancer cell of extracts and compounds isolated from Hyptis pectinata (L.) poit

Hyptis pectinata is a herb popularly used in Brazil for the treatment of inflammations, pain, bacterial infections and cancer. In the present study, inflorescences (MPIn), leaves (MPL), branches (MPB), root (MPR) extracts and three compounds isolated from MPIn were assayed against breast tumor cell lines. The structures of the three compounds (pectinolide J, hyptolide and pectinolide E) were determined by means of spectroscopic analysis. Pectinolide J was isolated for the first time. The MPIn, MPL and MPR exhibited specific antiproliferative activity on tumor cell lines when compared to normal cell lines with IC50 of 52.01 +/- 0.64, 45.91 +/- 0.02 mu g/mL and 82.84 +/- 0.03 mu g/mL, respectively. Although the isolated substances did not present good antiproliferative activity, when the three were associated, a greater biological effect was observed, suggesting a synergistic effect. Hyptolide (5.6 +/- 0.4 mu g/mL) showed IC50 sufficiently low to be considered as a drug prototype341102109CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES

The specificity of frutalin lectin using biomembrane models

Frutalin is a homotetrameric alpha-D-galactose (D-Gal)-binding lectin that activates natural killer cells in vitro and promotes leukocyte migration in vivo. Because lectins are potent lymphocyte stimulators, understanding the interactions that occur between them and cell surfaces can help to the action mechanisms involved in this process. In this paper, we present a detailed investigation of the interactions of frutalin with phospho- and glycolipids using Langmuir monolayers as biomembrane models. The results confirm the specificity of frutalin for D-Gal attached to a biomembrane. Adsorption of frutalin was more efficient for the galactose polar head lipids, in contrast to the one for sulfated galactose, in which a lag time is observed, indicating a rearrangement of the monolayer to incorporate the protein. Regarding ganglioside GM1 monolayers, lower quantities of the protein were adsorbed, probably due to the farther apart position of D-galactose from the interface. Binary mixtures containing galactocerebroside revealed small domains formed at high lipid packing in the presence of frutalin, suggesting that lectin induces the clusterization and the forming of domains in vitro, which may be a form of receptor internalization. This is the first experimental evidence of such lectin effect, and it may be useful to understand the mechanism of action of lectins at the molecular level. (C) 2010 Elsevier B.V. All rights reserved.FAPESPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

[10]-gingerol is a potent inhibitor of breast cancer metastasis in vivo

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