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https://www.readbyqxmd.com/read/28693187/salinomycin-inhibits-canine-mammary-carcinoma-in-vitro-by-targeting-cancer-stem-cells
#1
Hongchao Du, Bin Zhou, Hong Zhang, Yipeng Jin, Di Zhang, Degui Lin
Salinomycin (SAL), a polyether ionophore antibiotic, has been demonstrated to selectively kill cancer stem cells (CSCs) in various types of human tumor. The aim of the present study was to investigate the effects of SAL on canine mammary CSCs. CSCs in canine mammary carcinoma cell lines (CMT7364 and CIPp) were identified using a sphere formation assay and flow cytometry. The chemoresistance, invasive potential and expression of stem cell-associated proteins of these spheres was then analyzed. This demonstrated that the spheres exhibited characteristics of CSCs, including a cluster of differentiation (CD)44(+)/CD24(-/low) phenotype, upregulation of Wnt/β-catenin signaling pathway-associated proteins and chemoresistance...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692437/codelivery-of-salinomycin-and-docetaxel-using-poly-d-l-lactic-co-glycolic-acid-poly-ethylene-glycol-nanoparticles-to-target-both-gastric-cancer-cells-and-cancer-stem-cells
#2
Lan Li, Dejun Cui, Limin Ye, Yu Li, Liyi Zhu, Lanqun Yang, Banjun Bai, Zhao Nie, Jie Gao, Yu Cao
Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of ∼140 nm with a narrow size distribution, high drug loading, and sustained drug release...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28688275/design-and-synthesis-of-conformationally-constrained-salinomycin-derivatives
#3
Wenxuan Zhang, Jun Wu, Bo Li, Xu Lian, Jie Xia, Qi Zhou, Song Wu
Two conformationally restricted salinomycin derivatives by tethering the hydroxyl groups at C1 and C20 with different chain length were designed and synthesized. The cyclic derivatives showed better biological activities than C1/C20 modified derivatives, indicating the importance of the compact conformation for the ion binding capacity. In addition, the length of the connective chain plays critical role in the biological activities, thus cyclic the derivative 7 preserved some pharmacological activity but derivative 5 with two carbon atom shorter chain showed significantly reduced activity...
June 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28676857/salinomycin-exerts-anticancer-effects-on-pc-3-cells-and-pc-3-derived-cancer-stem-cells-in-vitro-and-in-vivo
#4
Yunsheng Zhang, Luogen Liu, Fang Li, Tao Wu, Hongtao Jiang, Xianxun Jiang, Xiaobo Du, Yi Wang
Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs). However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28665718/relationship-between-broiler-body-weights-eimeria-maxima-gross-lesion-scores-and-microscores-in-three-anticoccidial-sensitivity-tests
#5
Miguel A Barrios, Manuel Da Costa, Emily Kimminau, Lorraine Fuller, Steven Clark, Gene Pesti, Robert Beckstead
Anticoccidial sensitivity tests (ASTs) serve to determine the efficacy of anticoccidial drugs against Eimeria field isolates in a controlled laboratory setting. The most commonly measured parameters are body weight gain, feed conversion ratio, gross intestinal lesion scores, and mortality. Due to the difficulty in reliably scoring gross lesion scores of Eimeria maxima , microscopic analysis of intestinal scrapings (microscores) can be used in the field to indicate the presence of this particular Eimeria. The goal of this study was to determine the relationship between E...
June 2017: Avian Diseases
https://www.readbyqxmd.com/read/28658520/cancer-stem-cell-and-bulk-cancer-cell-active-copper-ii-complexes-with-vanillin-schiff-base-derivatives-and-naproxen
#6
Chunxin Lu, Arvin Eskandari, Paul Cressey, Kogularamanan Suntharalingam
Four copper(II) complexes, 1-4 containing regioisomeric vanillin Schiff base derivatives ((E)-5/4/3/2-methoxy-2-(((2-(methylthio)ethyl)imino)methyl)phenol) and the nonsteroidal anti-inflammatory drug (NSAID), naproxen, were synthesised and characterised. All complexes effectively cleave DNA in cell-free systems, with 4 displaying the highest nuclease activity. DNA binding studies suggest that 4 binds to DNA via the grooves prior to inducing oxidative DNA cleavage. Three of the complexes (1, 3, and 4) indiscriminately kill cancer stem cell (CSC)-enriched cells (HMLER-shEcad) and bulk cancer cells (HMLER) at micromolar concentrations...
June 28, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28656701/salinomycin-overcomes-acquired-tamoxifen-resistance-through-aib1-and-inhibits-cancer-cell-invasion-in-endocrine-resistant-breast-cancer
#7
Suwisit Manmuan, Nithidol Sakunrangsit, Wannarasmi Ketchart
Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus. It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF-7/LCC2 and MCF-7/LCC9 cell lines which are well-established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay...
June 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28651817/angiogenesis-and-cancer-stem-cells-new-perspectives-on-therapy-of-ovarian-cancer
#8
REVIEW
Anna Markowska, Stefan Sajdak, Janina Markowska, Adam Huczyński
Failure in ovarian cancer therapy, following cytoreduction and chemotherapy, is related to the presence of cancer stem cells - a small subpopulation of cells resistant to chemotherapy and irradiation - in the tumour which may cause cancer relapse and manifestation of metastases. Therapies targeted at Cancer Stem Cells (CSCs), such as those employing metformin (a drug used in the treatment of diabetes type II) and salinomycin, an antibiotic isolated from Streptococcus albus bacteria, seem promising. Anti-angiogenic therapy with bevacizumab was found to be effective in all phases of ovarian cancer treatment...
June 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28627601/an-in%C3%A2-vitro-study-on-the-effects-of-the-combination-of-salinomycin-with-cisplatin-on-human-gastric-cancer-cells
#9
Zuwen Zhang, Jumei Zhao, Qiuxia Pang, Aihong Wang, Meini Chen, Xiaoli Wei
The present study aimed to investigate the anticancer effects of cisplatin (DDP) combined with salinomycin (SAL) on the gastric cancer cell line SGC‑7901, as well as to explore the mechanisms underlying their actions. An MTT assay was used to evaluate the inhibitory effects of SAL, DDP and their combination on gastric cancer cell proliferation. Morphological alterations of cancer cells following treatment were observed under an inverted phase‑contrast microscope and a fluorescence microscope. Cell cycle progression and apoptosis were analyzed using flow cytometry...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627587/effects-of-salinomycin-and-17%C3%A2-aag-on-proliferation-of-human-gastric-cancer-cells-in%C3%A2-vitro
#10
Zuwen Zhang, Jumei Zhao, Zhikuan Mi, Qiuxia Pang, Aihong Wang, Meini Chen, Xiaobin Liu, Xiaoli Wei, Tao Liu
The aim of the present study was to investigate the effects and mechanisms of 17‑AAG combined with salinomycin treatment on proliferation and apoptosis of the SGC‑7901 gastric cancer cell line. An MTT assay was used to detect the proliferation of SGC‑7901 cells. Morphological alterations of cells were observed under inverted phase‑contrast and fluorescence microscopes. Cell cycle and apoptosis were assessed by flow cytometry analysis. The protein expression of nuclear factor (NF)‑κB p65 and Fas‑ligand (L) were evaluated by immunocytochemistry...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28613094/an-iron-hand-over-cancer-stem-cells
#11
Ahmed Hamaï, Tatiana Cañeque, Sebastian Müller, Trang Thi Mai, Antje Hienzsch, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez
The paradigm of cancer stem cells (CSCs) defines the existence of cells exhibiting self-renewal and tumor-seeding capacity. These cells have been associated with tumor relapse and are typically resistant to conventional chemotherapeutic agents. Over the past decade, chemical biology studies have revealed a significant number of small molecules able to alter the proliferation of these cells in various settings. The natural product salinomycin has emerged as the most promising anti-CSC agent. However, an explicit mechanism of action has not yet been characterized, in particular due to the pleiotropic responses salinomycin is known for...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28605700/a-novel-resveratrol-salinomycin-combination-sensitizes-er-positive-breast-cancer-cells-to-apoptosis
#12
Rajkumar Venkatadri, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
BACKGROUND: Resveratrol is a dietary compound that has been widely reported for its anticancer activities. However, successful extrapolation of its effects to pre-clinical studies is met with limited success due to inadequate bioavailability. We investigated the potential of combination therapy to improve the efficacy of resveratrol in a more physiologically relevant dose range. METHODS: The effect of resveratrol on canonical Wnt signaling was evaluated by Western blotting...
April 7, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28556445/induction-of-necroptosis-in-cancer-stem-cells-using-a-nickel-ii-dithiocarbamate-phenanthroline-complex
#13
Marie Flamme, Paul B Cressey, Chunxin Lu, Peter M Bruno, Arvin Eskandari, Michael T Hemann, Graeme Hogarth, Kogularamanan Suntharalingam
The cytotoxic properties of a series of nickel(II)-dithiocarbamate phenanthroline complexes is reported. The complexes 1-6 kill bulk cancer cells and cancer stem cells (CSCs) with micromolar potency. Two of the complexes, 2 and 6, kill twice as many breast cancer stem cell (CSC)-enriched HMLER-shEcad cells as compared to breast CSC-depleted HMLER cells. Complex 2 inhibits mammosphere formation to a similar extent as salinomycin (a CSC-specific toxin). Detailed mechanistic studies suggest that 2 induces CSC death by necroptosis, a programmed form of necrosis...
May 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28524116/inhibition-of-autophagy-promotes-salinomycin-induced-apoptosis-via-reactive-oxygen-species-mediated-pi3k-akt-mtor-and-erk-p38-mapk-dependent-signaling-in-human-prostate-cancer-cells
#14
Kwang-Youn Kim, Kwang-Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Sul-Gi Park, Young Woo Kim, Young-Kyo Seo, Jin-Yeul Ma, Soon-Cheol Ahn
Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28498472/salinomycin-induces-endoplasmic-reticulum-stress%C3%A2-mediated-autophagy-and-apoptosis-through-generation-of-reactive-oxygen-species-in-human-glioma-u87mg-cells
#15
Sun-Nyoung Yu, Sang-Hun Kim, Kwang-Youn Kim, Jae-Hoon Ji, Young-Kyo Seo, Hak Sun Yu, Soon-Cheol Ahn
Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell apoptosis in human cancer cells displaying multiple mechanisms of drug resistance. In the present study, we explored the impact of salinomycin on the apoptosis and autophagy as well as the correlation between those effects and endoplasmic reticulum (ER) stress molecular mechanisms in human glioma U87MG cells. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed using flow cytometry. In addition, expression levels of apoptosis-, autophagy- and ER stress-related proteins were determined by western blotting...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28455615/enhancement-of-antibiotic-productions-by-engineered-nitrate-utilization-in-actinomycetes
#16
Sitong Meng, Hang Wu, Lei Wang, Buchang Zhang, Linquan Bai
Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved...
July 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28454878/salinomycin-acts-through-reducing-akt-dependent-thymidylate-synthase-expression-to-enhance-erlotinib-induced-cytotoxicity-in-human-lung-cancer-cells
#17
Chun-Liang Tung, Jyh-Cheng Chen, Chia-Hung Wu, Yi-Shuan Peng, Wen-Ching Chen, Hao-Yu Zheng, Yi-Jun Jian, Chia-Li Wei, Ya-Ting Cheng, Yun-Wei Lin
Erlotinib (Tarceva(R)) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in the treatment of human non-small cell lung cancer (NSCLC). Salinomycin, a polyether antibiotic, has been promising a novel therapeutic agent for lung cancer, and down-regulated the expression of thymidylate synthase (TS) in NSCLC cell lines. Previous study showed that against EGFR and TS was strongly synergistic cytotoxicity in NSCLC cells. In this study, we showed that erlotinib (1.25-10μM) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell carcinoma H1703 and adenocarcinoma H1975 cells...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28453992/salinomycin-overcomes-radioresistance-in-nasopharyngeal-carcinoma-cells-by-inhibiting-nrf2-level-and-promoting-ros-generation
#18
Gong Zhang, Wenjun Wang, Chunxiao Yao, Jinjin Ren, Shuping Zhang, Muyuan Han
Radiotherapy is the most important treatment for nasopharyngeal carcinoma (NPC). Radioresistant cancer cells have been shown to potentially result in residual disease that can lead to recurrence and metastasis. Salinomycin (SAL) has been identified as a promising anticancer drug during chemical screening, but it is unclear whether SAL plays a role in radioresistance. The nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant system. There are currently numerous data indicating that Nrf2 has an important role in cancer radioresistance...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28440698/therapeutic-peg-ceramide-nanomicelles-synergize-with-salinomycin-to-target-both-liver-cancer-cells-and-cancer-stem-cells
#19
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...
May 2017: Nanomedicine
https://www.readbyqxmd.com/read/28415776/targeting-protein-homeostasis-with-nelfinavir-salinomycin-dual-therapy-effectively-induces-death-of-mtorc1-hyperactive-cells
#20
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
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