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Cancer multidrug resistance

A M Quílez, M A Fernández-Arche, M D García-Giménez, R De la Puerta
ETHNO-PHARMACOLOGICAL RELEVANCE: Annona species (Annonaceae) have long been used as traditional herbal medicines by native peoples in tropical areas. In different countries they are used against a large variety of illnesses, such as parasitic and infectious diseases, cancer, diabetes, peptic ulcers, and mental disorders. AIM OF THE STUDY: This review aims to achieve a comprehensive understanding of the research conducted so far on the local and traditional uses, pharmacological activities, mechanism of actions of active compounds, toxicity, and possible interactions with other drugs of the Annona species...
June 19, 2018: Journal of Ethnopharmacology
Luming Xu, Jia Liu, Jiangbo Xi, Qilin Li, Bingcheng Chang, Xianming Duan, Guobin Wang, Shuai Wang, Zheng Wang, Lin Wang
Despite the therapeutic usefulness of near-infrared irradiation (NIR)-induced potent photothermal effects (PTE) and photodynamic effects (PDE), they inevitably damage normal tissues, often posing threat to life when treating tumors adjacent to key organs or major blood vessels. In this study, the frequently overlooked, "weak" PTE and PDE (no killing capability) are employed to synergize chemotherapy against multidrug resistance (MDR) without impairing normal tissues. An NIR-responsive nanosystem, gold (Au)-nanodot-decorated hollow carbon nanospheres coated with hyaluronic acid, is synthesized as a doxorubicin (DOX) carrier with excellent photothermal and photodynamic properties...
June 21, 2018: Small
Augustin Le Naour, Renaud Mevel, Benoit Thibault, Elise Courtais, Elodie Chantalat, Jean Pierre Delord, Bettina Couderc, Julie Guillermet-Guibert, Alejandra Martinez
Background: Ovarian cancer is associated with poor prognostic outcome due to late diagnosis and to intrinsic and acquired resistance to platinum-based chemotherapy in a large number of patients. This chemoresistance is acquired through the peritoneal and ascites microenvironment by several released factors, such as IL-6,. Preclinical studies have implicated the activation of PI3K pathway in chemoresistance, showing it to extend tumor cell survival and modulate multidrug resistance. We aimed to evaluate the implication of the p110 alpha PI3K subunit in ovarian cancer chemoresistance acquisition, and to evaluate whether the STAT3 pathway can mediate resistance to PI3K inhibitors through secretion of IL6...
June 5, 2018: Oncotarget
Changlong Li, Hezhen Wu, Yanfang Yang, Jianwen Liu, Zhenwen Chen
Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 ( MDR1 ) and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by MDR1 ) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the MDR1 gene promoter...
June 2018: Oncology Letters
Min Yang, Nurit Livnat Levanon, Burçin Acar, Burcu Aykac Fas, Gal Masrati, Jessica Rose, Nir Ben-Tal, Turkan Haliloglu, Yongfang Zhao, Oded Lewinson
ATP-binding cassette (ABC) transporters use the energy of ATP hydrolysis to move molecules through cellular membranes. They are directly linked to human diseases, cancer multidrug resistance, and bacterial virulence. Very little is known of the conformational dynamics of ABC transporters, especially at the single-molecule level. Here, we combine single-molecule spectroscopy and a novel molecular simulation approach to investigate the conformational dynamics of the ABC transporter BtuCD. We observe a single dominant population of molecules in each step of the transport cycle and tight coupling between conformational transitions and ligand binding...
July 2018: Nature Chemical Biology
Tingting Lv, Liang Xu, Guolin Wu, Cailong Li, Yibo Wen, Tao Zhang, Haijun Chen, Yu Gao
Chemotherapy is currently one of the promising therapeutic methods for non-small-cell lung cancer (NSCLC), but the emergence of multidrug resistance (MDR) is the greatest obstacle to efficient drug delivery for successful chemotherapy. Nanotechnology-based drug delivery holds great promise to promote intracellular drug delivery to reverse MDR. In this work, we used our previously synthesized ursolic acid (UA) derivative, FZU-03,010 (F3), to prepare nanodrugs of F3 with different architectures and study the role of the structure on the physiochemical properties and the biological effects against A549 and its PTX-resistant A549/PTX lung cancer cells...
June 13, 2018: European Journal of Pharmaceutical Sciences
Jiajia Dong, Olajide E Olaleye, Rongrong Jiang, Jing Li, Chuang Lu, Feifei Du, Fang Xu, Junling Yang, Fengqing Wang, Weiwei Jia, Chuan Li
BACKGROUND AND PURPOSE: Intravenous glycyrrhizin, having anti-inflammatory and hepatoprotective properties, is incorporated into the management of liver diseases in China. This investigation was designed to elucidate the molecular mechanism underlying hepatobiliary excretion of glycyrrhizin and to investigate its potential for drug-drug interactions on organic anion-transporting polypeptides (OATP)1B. EXPERIMENTAL APPROACH: Human hepatic transporters were characterized for glycyrrhizin at the cellular and vesicular levels and compared with rat hepatic transporters...
June 16, 2018: British Journal of Pharmacology
Agata Mlynska, Egle Povilaityte, Inga Zemleckaite, Karolina Zilionyte, Marius Strioga, Jan Krasko, Neringa Dobrovolskiene, Mei-Wen Peng, Birute Intaite, Vita Pasukoniene
PROBLEM: Development of platinum resistance in ovarian cancer is mediated by both cancer cells and tumor microenvironment. Activation of epithelial-mesenchymal transition program in cancer cells may lead to enrichment for resistant clones. These processes can be affected by tumor-associated macrophages, a highly plastic population of cells that participate in tumor progression and response to treatment by shaping the microenvironment. We aimed to study how platinum resistance influences the crosstalk between macrophages and ovarian cancer cells...
June 14, 2018: American Journal of Reproductive Immunology: AJRI
Edith Lahner, Marilia Carabotti, Bruno Annibale
Helicobacter pylori (Hp) is a major human pathogen causing chronic, progressive gastric mucosal damage and is linked to gastric atrophy and cancer. Hp-positive individuals constitute the major reservoir for transmission of infection. There is no ideal treatment for Hp. Hp infection is not cured by a single antibiotic, and sometimes, a combined treatment with three or more antibiotics is ineffective. Atrophic gastritis (AG) is a chronic disease whose main features are atrophy and/or intestinal metaplasia of the gastric glands, which arise from long-standing Hp infection...
June 14, 2018: World Journal of Gastroenterology: WJG
Hao Chen, Shuguo Li, Shuibin Wang, Weiping Li, Ning Bao, Wenbin Ai
The emergence of multidrug resistance (MDR) is a significant challenge in breast carcinoma chemotherapy. Kokusaginine isolated from Dictamnus dasycarpus Turcz. has been reported to show cytotoxicity in several human cancer cell lines including breast cancer cells MCF-7. In this study, kokusaginine showed the potent inhibitory effect on MCF-7 multidrug resistant subline MCF-7/ADR and MDA-MB-231 multidrug resistant subline MDA-MB-231/ADR. Kokusaginine markedly induced apoptosis in a concentration-dependent manner in MCF-7/ADR cells...
May 30, 2018: Bioorganic & Medicinal Chemistry Letters
Jing Xin, Sijia Wang, Jing Wang, Jiazhuang Wang, Lei Fu, Lijian Shen, Zhenxi Zhang, Cuiping Yao
The poor cell membrane penetration ability of photosensitizers resulted in the limited antitumor effect, thereby hampered their potential in clinical translation. The high toxic side effect and multidrug resistance of chemotherapeutic agents during in clinical chemical therapy should be resolved. Nanosystem integrated with photosensitizer and novel targeting chemotherapy agent may be an effective strategy for overcoming clinical or preclinical drawbacks of monotherapy and enhancing therapeutic effect. Therefore, a nanosized micelle F127 integrated with Apogossypolone (ApoG2) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) (referred as F127-ApoG2@AlPcS4) was synthesized to induce the cell death quickly for reducing the risk of resistance and enhancing gastric cancer therapeutic efficiency by combining AlPcS4/photodynamic therapy and ApoG2/chemotherapy...
August 1, 2018: Journal of Biomedical Nanotechnology
Z Kozovska, A Patsalias, V Bajzik, E Durinikova, L Demkova, S Jargasova, B Smolkova, J Plava, L Kucerova, M Matuskova
BACKGROUND: Recent evidence in cancer research, developed the notion that malignant tumors consist of different subpopulations of cells, one of them, known as cancer stem cells, being attributed many important properties such as enhanced tumorigenicity, proliferation potential and profound multidrug resistance to chemotherapy. Several key stem cells markers were identified in colon cancer. In our study we focused on the aldehyde dehydrogenase type 1 (ALDH1) expression in colon cancer-derived cell lines HT-29/eGFP, HCT-116/eGFP and LS-180/eGFP, and its role in the chemoresistance and tumorigenic potential...
June 15, 2018: BMC Cancer
Min Chen, Xiaolong Liang, Chuang Gao, Ranran Zhao, Nisi Zhang, Shumin Wang, Wen Chen, Bo Zhao, Jinrui Wang, Zhifei Dai
Multidrug resistance remains a major obstacle to efficient chemotherapy of colorectal cancer. Herein, an efficient drug delivery and combination therapeutic strategy is proposed based on porphyrin/camptothecin-fluxoridine triad microbubbles (PCF-MBs), which show remarkably high drug loading content, highly stable co-delivery drug combinations and no premature release. The triad PCF-MBs can act not only as a contrast agent for ultrasound/fluorescence bi-modal imaging but also a multi-modal therapeutic agent for synergetic combined chemo-photodynamic therapy...
June 14, 2018: ACS Nano
Juke Ma, Zhenghua Lv, Xiuxiu Liu, Xianfang Liu, Wei Xu
Multidrug resistance (MDR) is a major impediment to cancer therapy. MG‑132 has been identified to be effective against MDR in several types of cancer. However, the mechanism of MG‑132 in head and neck squamous cell carcinomas remains unknown. Based on our previous study, the present detected P‑gp and P‑gp expression in hypopharyngeal carcinoma FaDu cells, revealing that their expression was lower than that observed in the MDR cell line FaDu/T. To reverse the MDR of FaDu/T cells, the present study introduced MG‑132 and demonstrated that the high expression of P‑gp/P‑gp in FaDu/T cells was attenuated in a time‑dependent manner...
June 6, 2018: Molecular Medicine Reports
Yueling Yuan, Peter Chiba, Tiange Cai, Richard Callaghan, Li Bai, Susan P C Cole, Yu Cai
In the present study, a lipid-polymer hybrid drug carrier system was developed to encapsulate psoralen (PSO), a multidrug resistance reversal agent and traditional Chinese medicine. Emphasis was focused the parameters that influence physicochemical characteristics, and then the drug release profile, stability, cytotoxicity and drug resistance reversal effect of the lipid-polymer hybrid nanoparticles (LPNs) were investigated. It was found that various formulation parameters affected NP size, drug loading (DL) and release characteristics...
June 14, 2018: Oncology Reports
Jarle Bruun, Anita Sveen, Rita Barros, Peter W Eide, Ina Eilertsen, Matthias Kolberg, Teijo Pellinen, Leonor David, Aud Svindland, Olli Kallioniemi, Marianne G Guren, Arild Nesbakken, Raquel Almeida, Ragnhild A Lothe
We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I-IV primary CRCs by gene expression (n=403) or immunohistochemistry (n=642) and in relation to 5-year relapse-free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines...
June 14, 2018: Molecular Oncology
Martin C Pearce, John T Gamble, Prasad R Kopparapu, Edmond F O'Donnell, Monica J Mueller, Hyo Sang Jang, Julie A Greenwood, Arnold C Satterthwait, Robert L Tanguay, Xiao-Kun Zhang, Siva Kumar Kolluri
Resistance to chemotherapy is a major cause of treatment failure and poor overall survival in patients with lung cancer. Identification of molecular targets present in resistant cancer cells is essential for addressing therapeutic resistance and prolonging lung cancer patient survival. Members of the B-cell lymphoma 2 (Bcl-2) family of proteins are associated with chemotherapeutic resistance. In this study, we found that pro-survival protein Bcl-2 is upregulated in paclitaxel resistant cells, potentially contributing to chemotherapy resistance...
May 25, 2018: Oncotarget
Fan Wu, Ming Zhang, Hanwen Lu, Dong Liang, Yaliang Huang, Yonghong Xia, Yuqing Hu, Shengqiang Hu, Jianxiu Wang, Xinyao Yi, Jun Zhang
The prematurea leakage of anticancer drugs during blood circulation may damage immune system, normal cells and tissues. Constructing targeted nanocarrier with pH, glutathione (GSH) and NIR triple-responsive property can effectively avoid the leakage of anticancer drugs before it arrives targeted site. In this paper, magnetic hollow porous carbon nanoparticles (MHPCNs) were successfully fabricated as nanocarrier. Poly(γ-glutamic acid) (PGA) was used to cap the pores of MHPCNs. Utilizing photothermal conversion property of carbon and iron oxide (Fe3O4) nanomaterials to perform photothermal therapy (PTT) to overcome multidrug-resistance (MDR) produced by chemotherapy...
June 12, 2018: ACS Applied Materials & Interfaces
Anna Hucke, Ga Young Park, Oliver B Bauer, Georg Beyer, Christina Köppen, Dorothea Zeeh, Christoph A Wehe, Michael Sperling, Rita Schröter, Marta Kantauskaitè, Yohannes Hagos, Uwe Karst, Stephen J Lippard, Giuliano Ciarimboli
Cancer treatment with platinum compounds is an important achievement of modern chemotherapy. However, despite the beneficial effects, the clinical impact of these agents is hampered by the development of drug resistance as well as dose-limiting side effects. The efficacy but also side effects of platinum complexes can be mediated by uptake through plasma membrane transporters. In the kidneys, plasma membrane transporters are involved in their secretion into the urine. Renal secretion is accomplished by uptake from the blood into the proximal tubules cells, followed by excretion into the urine...
2018: Frontiers in Chemistry
Angelika Długosz, Katarzyna Gach-Janczak, Jacek Szymański, Dariusz Deredas, Tomasz Janecki, Anna Janecka
BACKGROUND: The development of multidrug resistance to chemotherapy remains a challenge in the treatment of cancer and is a major factor causing failure of many forms of chemotherapy. The ATP binding cassette (ABC) family of proteins are efflux pumps that transport various potentially dangerous substances out of the cells. Several of the ABC transporters are related to chemoresistance, as the rapidly dividing malignant cells use them to protect themselves from medical interventions. Inhibitors of ABC transporters have the potential to enhance the efficacy of anticancer drugs...
January 10, 2018: Pharmacological Reports: PR
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