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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28345463/computational-and-mechanistic-studies-on-the-effect-of-galactoxyloglucan-imatinib-nanoconjugate-in-imatinib-resistant-k562-cells
#1
Alphy Rose James, B S Unnikrishnan, R Priya, Manu M Joseph, T K Manojkumar, K Raveendran Pillai, R Shiji, G U Preethi, P Kusumakumary, T T Sreelekha
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344555/drug-repurposing-of-the-anthelmintic-niclosamide-to-treat-multidrug-resistant-leukemia
#2
Sami Hamdoun, Philipp Jung, Thomas Efferth
Multidrug resistance, a major problem that leads to failure of anticancer chemotherapy, requires the development of new drugs. Repurposing of established drugs is a promising approach for overcoming this problem. An example of such drugs is niclosamide, a known anthelmintic that is now known to be cytotoxic and cytostatic against cancer cells. In this study, niclosamide showed varying activity against different cancer cell lines. It revealed better activity against hematological cancer cell lines CCRF-CEM, CEM/ADR5000, and RPMI-8226 compared to the solid tumor cell lines MDA-MB-231, A549, and HT-29...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#3
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#4
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28337331/light-regulated-no-release-as-a-novel-strategy-to-overcome-doxorubicin-multidrug-resistance
#5
Konstantin Chegaev, Aurore Fraix, Elena Gazzano, Gamal Eldein F Abd-Ellatef, Marco Blangetti, Barbara Rolando, Sabrina Conoci, Chiara Riganti, Roberta Fruttero, Alberto Gasco, Salvatore Sortino
Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28335655/the-therapeutic-potential-of-targeting-abc-transporters-to-combat-multi-drug-resistance
#6
Piyush Bugde, Riya Biswas, Fabrice Merien, Jun Lu, Dong-Xu Liu, Mingwei Chen, Shufeng Zhou, Yan Li
Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters...
March 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28333459/6-oh-phenanthroquinolizidine-alkaloid-and-its-derivatives-exert-potent-anticancer-activity-by-delaying-s-phase-progression
#7
Yuxiu Liu, Lihua Qing, Chuisong Meng, Jiajie Shi, Yan Yang, Ziwen Wang, Guifang Han, Yi Wang, Jian Ding, Ling-Hua Meng, Qingmin Wang
To discover new phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anticancer drug candidates, non-natural 6-O-desmethylcryptopleurine (2) and its derivatives were prepared. Most of the new compounds exhibited potent antiproliferative activity against A549 and BEL-7402 cells, with the lowest IC50 being 3 nM. Optically pure 2-R was further evaluated against a panel of 30 cancer cell lines and found to inhibit the proliferation of all tested cell lines, including three multidrug-resistant cell lines, with an average IC50 value of 2...
March 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28329730/synthesis-of-novel-quinoline-based-4-5-dihydro-1h-pyrazoles-as-potential-anticancer-antifungal-antibacterial-and-antiprotozoal-agents
#8
Jonathan Ramírez-Prada, Sara M Robledo, Iván D Vélez, María Del Pilar Crespo, Jairo Quiroga, Rodrigo Abonia, Alba Montoya, Laura Svetaz, Susana Zacchino, Braulio Insuasty
A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC50 values ranging from 2...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28329693/lanthanide-integrated-supramolecular-polymeric-nanoassembly-with-multiple-regulation-characteristics-for-multidrug-resistant-cancer-therapy
#9
Weihong Jin, Qiwen Wang, Min Wu, Yang Li, Guping Tang, Yuan Ping, Paul K Chu
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes...
March 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28328815/strobe-compliant-integrin-through-focal-adhesion-involve-in-cancer-stem-cell-and-multidrug-resistance-of-ovarian-cancer
#10
Luwei Wei, Fuqiang Yin, Wei Zhang, Li Li
Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327716/chemo-photodynamic-combined-gene-therapy-and-dual-modal-cancer-imaging-achieved-by-ph-responsive-alginate-chitosan-multilayer-modified-magnetic-mesoporous-silica-nanocomposites
#11
Hong Yang, Yin Chen, Zhongyuan Chen, Yue Geng, Xiaoxue Xie, Xue Shen, Tingting Li, Shun Li, Chunhui Wu, Yiyao Liu
Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance...
March 22, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28323029/the-dopamine-d3-receptor-antagonists-pg01037-ngb2904-sb277011a-and-u99194-reverse-abcg2-transporter-mediated-drug%C3%A2-resistance-in-cancer-cell-lines
#12
Noor Hussein, Haneen Amawi, Chandrabose Karthikeyan, F Scott Hall, Roopali Mittal, Piyush Trivedi, Charles R Ashby, Amit K Tiwari
The ATP - binding cassette (ABC) family G2 (ABCG2) transporters are known to produce multidrug resistance (MDR) in cancer, thereby limiting the clinical response to chemotherapy. Molecular modeling data indicated that certain dopamine (DA) D3 receptor antagonists had a significant binding affinity for ABCG2 transporter. Therefore, in this in vitro study, we determined the effect of the D3 receptor antagonists PG01037, NGB2904, SB277011A, and U99194 on MDR resulting from the overexpression of ABCG2 transporters...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28321609/the-cytotoxic-action-of-cytochrome-c-cardiolipin-nanocomplex-cyt-cl-on-cancer-cells-in-culture
#13
Yury A Vladimirov, Can Sarisozen, Georgy K Vladimirov, Nina Filipczak, Anastasia M Polimova, Vladimir P Torchilin
PURPOSE: The effect of existing anti-cancer therapies is based mainly on the stimulation of apoptosis in cancer cells. Here, we have demonstrated the ability of a catalytically-reactive nanoparticle-based complex of cytochrome c with cardiolipin (Cyt-CL) to induce the apoptosis and killing of cancer cells in a monolayer cell culture. METHODS: Cyt-CL nanoparticles were prepared by complexing CytC with different molar excesses of CL. Following characterization, cytotoxicity and apoptosis inducing effects of nanoparticles were investigated...
March 20, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28315369/resveratrol-as-mdr-reversion-molecule-in-breast-cancer-an-overview
#14
REVIEW
Nafiseh Sadat Alamolhodaei, Aristidis M Tsatsakis, Mohammad Ramezani, A Wallace Hayes, Gholamreza Karimi
Breast cancer is the most common cause of cancer mortality among women worldwide; therefore, a strategy to defeat breast cancer is an extremely important medical issue. One of the major challenges in this regard is multidrug resistance (MDR). Resveratrol, a well-known phytoestrogen, may be helpful as part of an overall strategy to defeat breast cancer. The mixed agonist and antagonist role of resveratrol for the estrogen receptor makes it a controversial but interesting molecule in cancer therapy, especially in hormone dependent cancers...
March 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28314481/benzophenones-and-xanthone-derivatives-from-garcinia-schomburgkiana-induced-p-glycoprotein-overexpression-in-human-colorectal-caco-2-cells-via-oxidative-stress-mediated-mechanisms
#15
Cherdsak Boonyong, Chutichot Pattamadilok, Rutt Suttisri, Suree Jianmongkol
BACKGROUND: Up-regulation of P-gp is an adaptive survival mechanism of cancer cells from chemotherapy. Three new phytochemicals including two benzophenones, guttiferone K (GK) and oblongifolin C (OC), and a xanthone, isojacaruebin (ISO), are potential anti-cancer agents. However, the capability of these compounds to increase multidrug-resistance (MDR) through P-gp up-regulation in cancer cells has not been reported. PURPOSE: This study was to investigate the effects of GK, OC and ISO on P-gp up-regulation in colorectal adenocarcinoma cells (Caco-2 cells)...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28303926/identification-of-the-metabolic-alterations-associated-with-the-multidrug-resistant-phenotype-in-cancer-and-their-intercellular-transfer-mediated-by-extracellular-vesicles
#16
Vanessa Lopes-Rodrigues, Alessio Di Luca, Justyna Mleczko, Paula Meleady, Michael Henry, Milica Pesic, Diana Cabrera, Sebastiaan van Liempd, Raquel T Lima, Robert O'Connor, Juan M Falcon-Perez, M Helena Vasconcelos
Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#17
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28302581/targeting-ets1-with-rnai-based-supramolecular-nanoassemblies-for-multidrug-resistant-breast-cancer-therapy
#18
Min Wu, Xingang Liu, Weihong Jin, Yongbing Li, Yang Li, Qinglian Hu, Paul K Chu, Guping Tang, Yuan Ping
Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically...
March 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#19
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28296906/anticancer-activity-of-a-novel-small-molecule-tubulin-inhibitor-stk899704
#20
Krisada Sakchaisri, Sun-Ok Kim, Joonsung Hwang, Nak Kyun Soung, Kyung Ho Lee, Tae Woong Choi, Yongjun Lee, Chan-Mi Park, Naraganahalli R Thimmegowda, Phil Young Lee, Bettaswamigowda Shwetha, Ganipisetti Srinivasrao, Thi Thu Huong Pham, Jae-Hyuk Jang, Hye-Won Yum, Young-Joon Surh, Kyung S Lee, Hwangseo Park, Seung Jun Kim, Yong Tae Kwon, Jong Seog Ahn, Bo Yeon Kim
We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1), and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines...
2017: PloS One
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