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Martina Tuttolomondo, Cinzia Casella, Pernille Lund Hansen, Ester Polo, Luciana M Herda, Kenneth A Dawson, Henrik J Ditzel, Jan Mollenhauer
Small interfering RNA (siRNA) is a promising molecule for gene therapy, but its therapeutic administration remains problematic. Among the recently proposed vectors, cell-penetrating peptides show great promise in in vivo trials for siRNA delivery. Human protein DMBT1 (deleted in malignant brain tumor 1) is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteria. Taking advantage of these properties, we investigated whether specific synthetic DMBT1-derived peptides could be used to formulate nanoparticles for siRNA administration...
September 15, 2017: Molecular Therapy. Nucleic Acids
Jiyong Hu, Yan Guo, Jin'an Zhao, Junshuai Zhang
Four benzimidazole-based Cu(II) complexes: Cu2(p-2-bmp)2Br4 (1), Cu2(p-2-bmp)2Cl4 (2), Cu2(p-2-bmb)2(DMF)2Br4·(CHCl3) (3), and Cu(p-2-bmb)(NO3)2·(CHCl3) (4) were isolated and characterized, where p-2-bmp is 1-((2-(pyridine-2-yl)-1H-benzoimidazol-1-yl)methyl)-1H-pyridine and p-2-bmb is 1-((2-(pyridin-2-yl)-1-benzoimidazol-1-yl)methyl)-1H-benzotriazole. Complexes 1 and 2 have binuclear configurations, 3 has a mononuclear structure, and 4has a one-dimensional (1-D) chain skeleton. To evaluate their potential anticancer effects on human carcinoma cells, anti-proliferation, DNA binding and cleavage, and apoptosis elicitation were examined...
September 5, 2017: Bioorganic & Medicinal Chemistry
Longfa Kou, Qing Yao, Sathish Sivaprakasam, Qiuhua Luo, Yinghua Sun, Qiang Fu, Zhonggui He, Jin Sun, Vadivel Ganapathy
l-Carnitine, obligatory for oxidation of fatty acids, is transported into cells by the Na(+)-coupled transporter OCTN2 and the Na(+)/Cl(-)-coupled transporter ATB(0,+). Here we investigated the potential of L-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) to deliver chemotherapeutic drugs into cancer cells by targeting the nanoparticles to both OCTN2 and ATB(0,+). The cellular uptake of LC-PLGA NPs in the breast cancer cell line MCF7 and the colon cancer cell line Caco-2 was increased compared to unmodified nanoparticles, but decreased in the absence of co-transporting ions (Na(+) and/or Cl(-)) or in the presence of competitive substrates for the two transporters...
November 2017: Drug Delivery
Benita S Katzenellenbogen, Yuechao Zhao, Mary J Laws, Valeria Sanabria Guillen, Yvonne Ziegler, Jian Min, Abhishek Sharma, Sung Hoon Kim, David Chu, Ben Ho Park, Steffi Oesterreich, Chengjian Mao, David J Shapiro, Kendall W Nettles, John A Katzenellenbogen
Many ERα-positive breast cancers develop resistance to endocrine therapy via mutation of estrogen receptors (ER) whose constitutive activation is associated with shorter patient survival. Because there is now a clinical need for new antiestrogens (AE) against these mutant ER, we describe here our development and characterization of three chemically novel AE that effectively suppress proliferation of breast cancer cells and tumors. Our AE are effective against wild type and Y537S and D538G ER, the two most commonly occurring constitutively active ER...
September 13, 2017: Cancer Research
Veronika Hanušová, Kateřina Caltová, Hana Svobodová, Martin Ambrož, Adam Skarka, Natálie Murínová, Věra Králová, Pavel Tomšík, Lenka Skálová
BACKGROUND: One approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. PURPOSE: The present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo...
September 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Akriti Kharbanda, Kristin Runkle, Wei Wang, Eric S Witze
Currently, there are no effective therapeutic strategies targeting Kras driven cancers, and therefore, identifying new targeted therapies and overcoming drug resistance have become paramount for effective long-term cancer therapy. We have found that reducing expression of the palmitoyl transferase DHHC20 increases cell death induced by the EGFR inhibitor gefitinib in Kras and EGFR mutant cell lines, but not MCF7 cells harboring wildtype Kras. We show that the increased gefitinib sensitivity in cancer cells induced by DHHC20 inhibition is mediated directly through loss of palmitoylation on a previously identified cysteine residue in the C-terminal tail of EGFR...
September 9, 2017: Biochemical and Biophysical Research Communications
M T Fernández-Ponce, A López-Biedma, C Sánchez-Quesada, L Casas, C Mantell, J J Gaforio, E J Martínez de la Ossa
Mango leaf tea has been traditionally used by different cultures to reduce inflammation in the body. There is evidence that chronic inflammation increases the risk of cancer. This study investigates the antitumoural effects of pressurized mango leaf extracts on minimally (MCF7) and highly invasive (MDA-MB-231) breast cancer cells as well as on non-tumourigenic cells (MCF10). Extracts showed protective properties against oxidation and cytotoxic effects against breast cancer cell lines, causing minor damage to non-carcinogenic cells...
September 11, 2017: Food & Function
L Leporini, L Giampietro, R Amororso, A Ammazzalorso, M Fantacuzzi, L Menghini, C Maccallini, C Ferrante, G Orlando, B De Filippis
Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine, which has been extensively studied for a wide range of biological effects. A large number of stilbene-containing derivatives have displayed antioxidant and antiproliferative activities on various cancer cell lines. In this study, a series of stilbene hybrids 1-9, previously reported as peroxisome proliferator-activated receptor (PPAR) agonists, were assessed at micromolar concentrations using MTT cell viability assay in C2C12 and MCF7 cell lines...
September 11, 2017: Journal of Biological Regulators and Homeostatic Agents
Sachin V Otari, Manoj Kumar, Muhammad Zahid Anwar, Nanasaheb D Thorat, Sanjay K S Patel, Dongjin Lee, Jai Hyo Lee, Jung-Kul Lee, Yun Chan Kang, Liaoyuan Zhang
This article presents novel, rapid, and environmentally benign synthesis method for one-step reduction and decoration of graphene oxide with gold nanoparticles (NAuNPs) by using thermostable antimicrobial nisin peptides to form a gold-nanoparticles-reduced graphene oxide (NAu-rGO) nanocomposite. The formed composite material was characterized by UV/Vis spectroscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM)...
September 8, 2017: Scientific Reports
Manuel A Ramos-Enríquez, Katherine Vargas-Romero, Lucie Rárová, Miroslav Strnad, Martin A Iglesias Arteaga
Benzylidenespirostanols were prepared by two-step synthesis including BF3•Et2O-catalyzed aldol condensation of several acetylated steroid sapogenins with benzaldehyde followed by saponification. The obtained compounds showed moderate cytotoxicity against three cancer cell lines (T-lymphoblastic leukemia cell line CEM, breast carcinoma cell line MCF7 and cervical carcinoma cell line HeLa) and normal human fibroblasts (BJ). The most active of the five tested substances was 3c (lowest IC50 for MCF7 cells 19...
September 5, 2017: Steroids
Mitra Shojania Feizabadi, Brandon Rosario, Marcos A V Hernandez
Recent studies suggested a link between diversity of beta tubulin isotypes in microtubule structures and the regulatory roles that they play not only on microtubules' intrinsic dynamic, but also on the translocation characteristics of some of the molecular motors along microtubules. Remarkably, unlike porcine brain microtubules, MCF7 microtubules are structured from a different beta tubulin distribution. These types of cancer microtubules show a relatively stable and slow dynamic. In addition, the translocation parameters of some molecular motors are distinctly different along MCF7 as compared to those parameters on brain microtubules...
September 5, 2017: Biochemical and Biophysical Research Communications
Manikanta Murahari, Karanam Vanitha Prakash, Godefridus J Peters, Y C Mayur
Hybrid systems of acridones with substituted pyrimidines were designed with an objective of discovering next generation anticancer agents targeting multiple mechanisms in the cancer cell. Hybrid compounds were synthesized by simple and convenient methods in the lab, characterized by NMR and Mass spectral methods and screened for cytotoxicity against A549 (lung), Hela (cervical), MCF7 (breast) and MDA-MB-231 (breast) cancer cell lines respectively. Evaluation of compounds for cell proliferation identified active compounds 11b, 11d and 11h against MCF7, MDA-MB-231 and A549 cell lines...
August 12, 2017: European Journal of Medicinal Chemistry
Carmelo Militello, Leonardo Rundo, Vincenzo Conti, Luigi Minafra, Francesco Paolo Cammarata, Giancarlo Mauri, Maria Carla Gilardi, Nunziatina Porcino
BACKGROUND: The current methodology for the Surviving Fraction (SF) measurement in clonogenic assay, which is a technique to study the anti-proliferative effect of treatments on cell cultures, involves manual counting of cell colony forming units. This procedure is operator-dependent and error-prone. Moreover, the identification of the exact colony number is often not feasible due to the high growth rate leading to the adjacent colony merging. As a matter of fact, conventional assessment does not deal with the colony size, which is generally correlated with the delivered radiation dose or the administered cytotoxic agent...
September 5, 2017: Computers in Biology and Medicine
Shaiya C Robinson, Nickett S Donaldson-Kabwe, Anna Dvorkin-Gheva, Joseph Longo, Lloyd He, Juliet M Daniel
Znf131 belongs to the family of POZ-ZF transcription factors, but, in contrast to most other characterized POZ-ZF proteins that function as transcriptional repressors, Znf131 acts as a transcriptional activator. Znf131 heterodimerizes with the POZ-ZF protein Kaiso, which itself represses a subset of canonical Wnt target genes, including the cell cycle regulator Cyclin D1. Herein, we report a possible role for Znf131 in Kaiso-mediated processes. Notably, we found that Znf131 associates with several Kaiso target gene promoters, including that of CCND1...
September 4, 2017: Biochemical and Biophysical Research Communications
Hasan Motaghi, Masoud Ayatollahi Mehrgardi, Philippe Bouvet
In the present study, a sensitive and selective signal-on method for aptamer based spectrofluorometric detection of cancer cells is introduced. AS1411, a nucleolin aptamer, is wrapped around water-soluble carbon dots and used as a probe for the detection of several types of cancer cells. Nucleolin, is overexpressed on the surface of cancer cells. Mouse breast 4T1, human breast MCF7, and human cervical HeLa cancer cells were selected as target cells, while human foreskin fibroblast cells HFFF-PI6 served as control cells...
September 5, 2017: Scientific Reports
Christopher F Theriau, O'Llenecia S Sauvé, Marie-Soleil Beaudoin, David C Wright, Michael K Connor
Obesity is clearly associated with an increased risk of breast cancer in postmenopausal women. The purpose was to determine if obesity alters the adipocyte adipokine secretion profile, thereby altering the adipose-dependent paracrine/endocrine growth microenvironment surrounding breast cancer cells (MCF7). Additionally, we determined whether resveratrol (RSV) supplementation can counteract any obesity-dependent effects on breast cancer tumor growth microenvironment. Obese ZDF rats received standard chow diet or diet supplemented with 200 mg/kg body weight RSV...
2017: PloS One
Mohammad A Ahmaditaba, Soraya Shahosseini, Bahram Daraei, Afshin Zarghi, Mohammad H Houshdar Tehrani
A new class of peptide derivatives possessing SO2 Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid-phase synthesis methodology, and evaluated as selective cyclooxygenase-2 (COX-2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX-2 inhibitor with a COX-2 selectivity index of >500. The structure-activity relationships (SARs) acquired indicated that compound 2a containing a 4-(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ring bearing amino acid in the second position and glutamic acid as the C-terminal amino acid can give the essential geometry to provide selective COX-2 inhibitory activity...
September 5, 2017: Archiv der Pharmazie
Daniel S Reynolds, Kristie M Tevis, William A Blessing, Yolonda L Colson, Muhammad H Zaman, Mark W Grinstaff
An abnormal multicellular architecture is a defining characteristic of breast cancer and, yet, most in vitro tumor models fail to recapitulate this architecture or accurately predict in vivo cellular responses to therapeutics. The efficacy of two front-line chemotherapeutic agents (paclitaxel and cisplatin) are described within three distinct in vitro models employing the triple-negative basal breast cancer cell line MDA-MB-231 and the luminal breast cancer cell line MCF7: a) a 3D collagen embedded multicellular spheroid tumor model, which reflects the architecture and cellular heterogeneity of tumors in vivo; b) a 3D collagen model with a single cell-type diffusely embedded; and c) a 2D monolayer...
September 4, 2017: Scientific Reports
Makoto Wakahara, Tomohiko Sakabe, Yasuaki Kubouchi, Keiko Hosoya, Yumi Hirooka, Yohei Yurugi, Kanae Nosaka, Tatsushi Shiomi, Hiroshige Nakamura, Yoshihisa Umekita
BACKGROUND/AIM: Maspin is known to be a tumor suppressor protein. Its nuclear localization and endogenous inhibition of histone deacetylase 1 (HDAC1) are considered crucial for its tumor suppressor activity. However, it remains unclear whether subcellular localization of maspin correlates with HDAC1 expression level in human breast cancer. PATIENTS AND METHODS: Immunohistochemical analyses were performed on 164 resected specimens of invasive breast carcinoma using antibodies for maspin and HDAC1...
September 2017: Anticancer Research
Hesham M Korashy, Zaid H Maayah, Fawaz E Al Anazi, Abdulaziz M Alsaad, Ibrahim O Alanazi, Osamah M Belali, Fahad O Al-Atawi, Aws Alshamsan
The tyrosine kinase inhibitor sunitinib was recently approved for use against gastrointestinal stromal tumors and advanced renal cell carcinoma. Yet, the protective effect of sunitinib against breast cancer has been poorly investigated. In this study, we investigated the antiproliferative and apoptogenic effects of sunitinib and the possible mechanism involved against the MCF7 human breast cancer cell line. Treatment of MCF7 cells with sunitinib caused concentration-dependent cell growth suppression due to apoptosis...
September 2017: Anticancer Research
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