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https://www.readbyqxmd.com/read/28440698/therapeutic-peg-ceramide-nanomicelles-synergize-with-salinomycin-to-target-both-liver-cancer-cells-and-cancer-stem-cells
#1
Meiping Wang, Fangyuan Xie, Xikai Wen, Han Chen, Hai Zhang, Junjie Liu, He Zhang, Hao Zou, Yuan Yu, Yan Chen, Zhiguo Sun, Xinxia Wang, Guoqing Zhang, Chuan Yin, Duxin Sun, Jie Gao, Beige Jiang, Yanqiang Zhong, Ying Lu
AIM: Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. MATERIALS & METHODS: The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. RESULTS: SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28415776/targeting-protein-homeostasis-with-nelfinavir-salinomycin-dual-therapy-effectively-induces-death-of-mtorc1-hyperactive-cells
#2
Elaine A Dunlop, Charlotte E Johnson, Marie Wiltshire, Rachel J Errington, Andrew R Tee
Uncontrolled cell growth in Tuberous Sclerosis Complex occurs due to inappropriate activation of mechanistic (mammalian) target of rapamycin complex 1 (mTORC1). The current therapy, rapamycin, produced promising clinical trial results, but patient tumours regrow if treatment is discontinued, revealing rapamycin has cytostatic properties rather than a cytotoxic effect. Taking advantage of the enhanced levels of endoplasmic reticulum (ER) stress present in TSC2-null cells, we investigated drug combinations producing a cytotoxic response...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402029/magnetic-solid-phase-extraction-based-on-carbon-nanotubes-for-the-determination-of-polyether-antibiotics-and-s-triazine-drug-residues-in-animal-food-with-lc-ms
#3
Xiaoxing Liu, Shuyu Xie, Tengteng Ni, Dongmei Chen, Xu Wang, Yuanhu Pan, Yulian Wang, Lingli Huang, Guyue Cheng, Wei Qu, Zhenli Liu, Yanfei Tao, Zonghui Yuan
Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide nanoparticles and carbon nanotubes, were prepared through a simple one-step synthesis method and subsequently applied to magnetic solid-phase extraction for the determination of polyether antibiotic and s-triazine drug residues in animal food coupled with liquid chromatography with tandem mass spectrometry. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The components within the nanocomposites endowed the material with high extraction performance and manipulative convenience...
April 12, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28401259/mechanism-of-salinomycin-overproduction-in-streptomyces-albus-as-revealed-by-comparative-functional-genomics
#4
Xiaojie Zhang, Chenyang Lu, Linquan Bai
The anticoccidial salinomycin is a polyketide produced by Streptomyces albus, and the high-yield strain BK 3-25 produces 18.0 g/L salinomycin under lab condition. In order to elucidate the overproduction mechanism, the genome of BK 3-25 was fully sequenced and compared with the wild-type DSM 41398. Strain BK 3-25 has a 75-kb large deletion, containing type-I polyketide gene cluster PKS-9, and 60 additional InDels and SNVs affecting 55 CDSs, including a 1-bp deletion in type-I PKS gene cluster PKS-6. Subsequently, individual or combined deletions of the 75-kb region and PKS-6 in the wild-type resulted in improved salinomycin yields from 2...
April 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28395993/salinomycin-attenuates-liver-cancer-stem-cell-motility-by-enhancing-cell-stiffness-and-increasing-f-actin-formation-via-the-fak-erk1-2-signalling-pathway
#5
Jinghui Sun, Qing Luo, Lingling Liu, Xianjiong Yang, Shunqin Zhu, Guanbin Song
Salinomycin has recently been identified as an antitumour drug for several types of cancer stem cell (CSC) treatments. However, the effects of salinomycin on the migratory and invasive properties of liver cancer stem cells (LCSCs) are unclear. In present study, we investigated the effect of salinomycin on the migration and invasion of LCSCs, and examined the molecular mechanisms underlying the anticancer effects of salinomycin. Here we showed that the migration and invasion of LCSCs were significantly suppressed in a salinomycin dose-dependent manner...
April 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28391864/a-simple-and-high-throughput-method-for-determination-and-confirmation-of-14-coccidiostats-in-poultry-muscle-and-eggs-using-liquid-chromatography-quadrupole-linear-ion-trap-tandem-mass-spectrometry-hplc-qqlit-ms-ms-validation-according-to-european-union-2002
#6
Fabiano Barreto, Cristina Ribeiro, Rodrigo Barcellos Hoff, Teresa Dalla Costa
A simple and fast quantitative and confirmatory multi-residue method was developed and validated for the determination of 14 coccidiostats residues in poultry muscle and eggs using liquid chromatography-tandem mass spectrometry (LC/MS-MS). The compounds were analyzed in a single run including lasalocid A, maduramicin, monensin, narasin, salinomycin, semduramicin, robenidine, diclazuril, toltrazuril, trimethoprim, clopidol, amprolium, diaveridine and nicarbazin (as the marker residue dinitrocarbanilide). A low-cost extraction and clean up procedure was optimized without the need of solid-phase extraction...
June 1, 2017: Talanta
https://www.readbyqxmd.com/read/28373437/salinomycin-induces-reactive-oxygen-species-and-apoptosis-in-aggressive-breast-cancer-cells-as-mediated-with-regulation-of-autophagy
#7
Kwang-Youn Kim, Kwang Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Deokjae Lee, Young Woo Kim, Kyung Tae Noh, Jin Yeul Ma, Young-Kyo Seo, Soon-Cheol Ahn
BACKGROUND/AIM: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism. MATERIALS AND METHODS: Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28358414/salinomycin-exhibits-anti-angiogenic-activity-against-human-glioma-in-vitro-and-in-vivo-by-suppressing-the-vegf-vegfr2-akt-fak-signaling-axis
#8
Yan-Ling Bi, Pei-Yan Mi, Shi-Jun Zhao, Heng-Ming Pan, Hui-Juan Li, Fei Liu, Lu-Rong Shao, Hui-Fang Zhang, Pu Zhang, Shi-Liang Jiang
Tumor angiogenesis plays a crucial role in tumor growth, progression and metastasis, and suppression of tumor angiogenesis has been considered as a promising anticancer strategy. Salinomycin (SAL), an antibiotic, displays novel anticancer potential against several human cancer cells in vitro and in vivo. However, little information concerning its anti-angiogenic properties is available. Therefore, the anti‑angiogenic effect of SAL and the underlying mechanism in human glioma were evaluated in the present study...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28349817/salinomycin-a-new-paradigm-in-cancer-therapy
#9
REVIEW
Jayant Dewangan, Sonal Srivastava, Srikanta Kumar Rath
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate-binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/β-catenin, Hedgehog, and Notch pathways of cancer progression...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28346100/robotic-mammosphere-assay-for-high-throughput-screening-in-triple-negative-breast-cancer
#10
P A Fitzpatrick, N Akrap, E M V Söderberg, H Harrison, G J Thomson, G Landberg
In order to identify novel treatment principles specifically affecting cancer stem cells in triple-negative breast cancer, we have developed a high-throughput screening method based on the mammosphere and anoikis resistance assays allowing us to screen compounds using a functional readout. The assay was validated against manual protocols and through the use of positive controls, such as the response to hypoxia and treatment with the known cancer stem cell-targeting compound salinomycin. Manual and robotic procedures were compared and produced similar results in cell handling, cell cultures, and counting techniques, with no statistically significant difference produced from either method...
February 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28340000/effects-of-feeding-original-xpc%C3%A2-to-broilers-with-a-live-coccidiosis-vaccine-under-industry-conditions-part-1-growth-performance-and-salmonella-inhibition
#11
S M Roto, S H Park, S I Lee, P Kaldhone, H O Pavlidis, S B Frankenbach, D R McIntyre, K Striplin, L Brammer, S C Ricke
Supplementation of poultry diets with Diamond V Original XPC™ (XPC) has been proposed as a means to ameliorate the commonly observed loss of appetite and depression of growth in birds given a live coccidiosis vaccine. A study was conducted to compare the effects on bird performance of a live coccidiosis vaccine in broilers, with and without the dietary inclusion of XPC (1.25 g/kg). Ross 708 male broilers (n = 1,280) were allocated to one of 4 feed treatments: cocci-vaccine (T1), cocci-vaccine + XPC (T2), cocci-vaccine + salinomycin in the grower diet only, (T3), and cocci-vaccine + salinomycin in the grower diet + XPC (T4)...
March 3, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339832/effects-of-feeding-original-xpc%C3%A2-to-broilers-with-a-live-coccidiosis-vaccine-under-industrial-conditions-part-2-cecal-microbiota-analysis
#12
S H Park, S Roto, H Pavlidis, D McIntyre, K Striplin, L Brammer, S C Ricke
Biological supplements in poultry feed are of continued interest due to the improvements in growth performance, protection from pathogen invasion, and benefits in overall host health. The fermentation metabolites of Diamond V Original XPC™ (XPC) have previously been shown to improve commercial performance and reduce Salmonella in poultry. The current study sought to characterize the cecal microbiota using culture-independent analysis based on 16S rRNA gene in Coccivac-D sprayed broilers supplemented with XPC and/or Salinomycin (SAL)...
March 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28298074/evaluation-of-growth-inhibitory-response-of-resveratrol-and-salinomycin-combinations-against-triple-negative-breast-cancer-cells
#13
Girish Rai, Shankar Suman, Sanjay Mishra, Yogeshwer Shukla
Resveratrol (RSVL) a dietary phytochemical showed to enhance the efficacy of chemotherapeutic drugs. Recently, Salinomycin (SAL) has gained importance as cancer therapeutic value for breast cancer (BC), however, its superfluxious toxicity delimits the utility. Taking the advantage of RSVL, the therapeutic efficacy of RSVL and SAL combination was studied in vitro and in vivo system. Firstly, the synergistic combination dose of RSVL and SAL was calculated and further, the efficacy was examined by wound healing, and Western blots analysis...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28293709/metabolic-perturbation-to-enhance-polyketide-and-nonribosomal-peptide-antibiotic-production-using-triclosan-and-ribosome-targeting-drugs
#14
Yukinori Tanaka, Masumi Izawa, Yoshikazu Hiraga, Yuya Misaki, Tomoko Watanabe, Kozo Ochi
Although transcriptional activation of pathwayspecific positive regulatory genes and/or biosynthetic genes is primarily important for enhancing secondary metabolite production, reinforcement of substrate supply, as represented by primary metabolites, is also effective. For example, partial inhibition of fatty acid synthesis with ARC2 (an analog of triclosan) was found to enhance polyketide antibiotic production. Here, we demonstrate that this approach is effective even for industrial high-producing strains, for example enhancing salinomycin production by 40%, reaching 30...
March 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28280366/salinomycin-repressed-the-epithelial-mesenchymal-transition-of-epithelial-ovarian-cancer-cells-via-downregulating-wnt-%C3%AE-catenin-pathway
#15
Rui Li, Taotao Dong, Chen Hu, Jingjing Lu, Jun Dai, Peishu Liu
Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Most patients are diagnosed in the advanced stage and have distant metastasis ultimately. Salinomycin has been demonstrated to reduce invasive capacity of multiple tumor cells. The objective of this study was to investigate the effects of salinomycin on EOC cells. The cell counting kit 8 (CCK-8) and Boyden chamber assays showed that salinomycin could effectively reduce the abilities of proliferation, migration and invasion in EOC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28262526/synthesis-and-biological-activity-of-salinomycin-hydroxamic-acid-conjugates
#16
Bo Li, Jun Wu, Wenxuan Zhang, Zhongwen Li, Gang Chen, Qi Zhou, Song Wu
Several salinomycin-hydroxamic acid conjugates were designed and synthesized. Most conjugates showed better antiproliferative activities than salinomycin in HT-29 colon cancer, HGC-27 gastric cancer, and especially in MDA-MB-231 triple-negative human breast cancer cells. These conjugates are stable in cell culture media, and they showed much better biological activities than the 1:1 physical mixture with hydroxamic acids and salinomycin. The better membrane permeability and hydrolysis rate of the conjugates may lead to the activity improvements...
April 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28179289/salinomycin-abolished-stat3-and-stat1-interactions-and-reduced-telomerase-activity-in-colorectal-cancer-cells
#17
Seyung S Chung, Debbie Adekoya, Ikechukwu Enenmoh, Orette Clarke, Piwen Wang, Marianna Sarkyssian, Yong Wu, Jaydutt V Vadgama
BACKGROUND: Colorectal cancer is the third leading cause of cancer-related mortality in most developed countries. This mortality is mainly due to the metastatic progression to the liver with frequent recurrence. Colorectal cancer remains a therapeutic challenge and this has intensified the search for new drug targets. In an effort to establish a novel targeted-therapy, we studied the molecular mechanisms of cancer stem cell inhibitor salinomycin. MATERIALS AND METHODS: Co-immunoprecipitation was performed to examine STAT3-STAT1 protein interactions...
February 2017: Anticancer Research
https://www.readbyqxmd.com/read/28177244/replacing-d-glucosamine-with-its-l-enantiomer-in-glycosylated-antitumor-ether-lipids-gaels-retains-cytotoxic-effects-against-epithelial-cancer-cells-and-cancer-stem-cells
#18
Makanjuola Ogunsina, Pranati Samadder, Temilolu Idowu, Gilbert Arthur, Frank Schweizer
We describe metabolically inert l-glucosamine-based glycosylated antitumor ether lipids (L-GAELs) that retain the cytotoxic effects of the D-GAELs including the ability to kill BT-474 breast cancer stem cells (CSCs). When compared to adriamycin, cisplatin, and the anti-CSC agent salinomycin, L-GAELs display superior activity to kill cancer stem cells (CSCs). Mode of action studies indicate that L-GAELs like the D-GAELs kill cells via an apoptosis-independent mechanism that was not due to membranolytic effects...
February 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28160001/influence-of-mycotoxin-binders-on-the-oral-bioavailability-of-tylosin-doxycycline-diclazuril-and-salinomycin-in-fed-broiler-chickens
#19
T De Mil, M Devreese, A Maes, S De Saeger, P De Backer, S Croubels
No abstract text is available yet for this article.
February 4, 2017: Poultry Science
https://www.readbyqxmd.com/read/28157306/mechanism-and-stereochemistry-of-polyketide-chain-elongation-and-methyl-group-epimerization-in-polyether-biosynthesis
#20
Xinqiang Xie, Ashish Garg, Chaitan Khosla, David E Cane
The polyketide synthases responsible for the biosynthesis of the polyether antibiotics nanchangmycin (1) and salinomycin (4) harbor a number of redox-inactive ketoreductase (KR(0)) domains that are implicated in the generation of C2-epimerized (2S)-2-methyl-3-ketoacyl-ACP intermediates. Evidence that the natural substrate for the polyether KR(0) domains is, as predicted, a (2R)-2-methyl-3-ketoacyl-ACP intermediate, came from a newly developed coupled ketosynthase (KS)-ketoreductase (KR) assay that established that the decarboxylative condensation of methylmalonyl-CoA with S-propionyl-N-acetylcysteamine catalyzed by the Nan[KS1][AT1] didomain from module 1 of the nanchangmycin synthase generates exclusively the corresponding (2R)-2-methyl-3-ketopentanoyl-ACP (7a) product...
March 1, 2017: Journal of the American Chemical Society
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