scholarly journals Development of benzochalcone derivatives as selective CYP1B1 inhibitors and anticancer agents

MedChemComm ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 1606-1614 ◽  
Author(s):  
Jinyun Dong ◽  
Guang Huang ◽  
Qijing Zhang ◽  
Zengtao Wang ◽  
Jiahua Cui ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Inhibitory Activity ◽  
Resistant Cell ◽  
Wild Type Cell ◽  
Drug Resistant ◽  
Wild Type ◽  
Drug Resistant Cell ◽  
Mcf 7

A series of benzochalcone derivatives have been synthesized and evaluated for CYP1 inhibitory activity and cytotoxic properties against wild type cell lines (MCF-7 and MDA-MB-231) and drug resistant cell lines (LCC6/P-gp and MCF-7/1B1).

Isoquinolinequinone N-oxides as anticancer agents effective against drug resistant cell lines

2020 ◽  
Vol 18 (3) ◽  
pp. 557-568 ◽  
Author(s):  
Ryan D. Kruschel ◽  
Alyah Buzid ◽  
Udaya B. Rao Khandavilli ◽  
Simon E. Lawrence ◽  
Jeremy D. Glennon ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Resistant Cell ◽  
Drug Resistant ◽  
Redox Active ◽  
Drug Resistant Cell

6- and 7-Substituted isoquinoline N-oxides are identified as redox active, adduct forming, anticancer agents and effective against drug resistant cell lines at nanomolar concentrations.

scholarly journals The significance of lumican expression in ovarian cancer drug-resistant cell lines

Oncotarget ◽  
2017 ◽  
Vol 8 (43) ◽  
pp. 74466-74478 ◽  
Author(s):  
Andrzej Klejewski ◽  
Karolina Sterzyńska ◽  
Karolina Wojtowicz ◽  
Monika Świerczewska ◽  
Małgorzata Partyka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Resistant Cell ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Drug Resistant Cell

Chromosome-mediated gene transfer of hydroxyurea resistance and amplification of ribonucleotide reductase activity

1983 ◽  
Vol 3 (6) ◽  
pp. 1053-1061
Author(s):  
W H Lewis ◽  
P R Srinivasan
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Ribonucleotide Reductase ◽  
Chinese Hamster ◽  
Fold Increase ◽  
Resistant Cell ◽  
Plating Efficiency ◽  
Wild Type Cell ◽  
Wild Type ◽  
Metaphase Chromosomes

Metaphase chromosomes purified from a hydroxyurea-resistant Chinese hamster cell line were able to transform recipient wild-type cells to hydroxyurea resistance at a frequency of 10(-6). Approximately 60% of the resulting transformant clones gradually lost hydroxyurea resistance when cultivated for prolonged periods in the absence of drug. One transformant was subjected to serial selection in higher concentrations of hydroxyurea. The five cell lines generated exhibited increasing relative plating efficiency in the presence of the drug and a corresponding elevation in their cellular content of ribonucleotide reductase. The most resistant cell line had a 163-fold increase in relative plating efficiency and a 120-fold increase in enzyme activity when compared with the wild-type cell line. The highly hydroxyurea-resistant cell lines had strong electron paramagnetic resonance signals characteristic of an elevated level of the free radical present in the M2 subunit of ribonucleotide reductase. Two-dimensional electrophoresis of cell-free extracts from one of the resistant cell lines indicated that a 53,000-dalton protein was present in greatly elevated quantities when compared with the wild-type cell line. These data suggest that the hydroxyurea-resistant cell lines may contain an amplification of the gene for the M2 subunit of ribonucleotide reductase.

scholarly journals Abstract No. 448 Comparison of electrochemotherapy and radiation for chemosensitization of drug resistant cell lines

2018 ◽  
Vol 29 (4) ◽  
pp. S190
Author(s):  
L. Vroomen ◽  
W. Vista ◽  
M. Fuijmori ◽  
J. Humm ◽  
S. Solomon ◽  
...  
Keyword(s):  
Cell Lines ◽  
Resistant Cell ◽  
Drug Resistant ◽  
Drug Resistant Cell

Next Generation XPO1 Inhibitor KPT-8602 for the Treatment of Drug-Resistant Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1818-1818 ◽  
Author(s):  
Joel G Turner ◽  
Jana L Dawson ◽  
Christopher L Cubitt ◽  
Erkan Baluglo ◽  
Steven Grant ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Ex Vivo ◽  
Single Agent ◽  
Resistant Cell ◽  
Drug Resistant ◽  
Newly Diagnosed ◽  
Induced Apoptosis ◽  
Drug Resistant Cell

Abstract Purpose Human multiple myeloma (MM) remains an incurable disease despite relatively effective treatments, including proteasome inhibitors, immunomodulator-based therapies, and high-dose chemotherapy with autologous stem cell rescue. New agents are needed to further improve treatment outcomes. In previous studies, we have shown that inhibitors of the nuclear export receptor XPO1, in combination with bortezomib, carfilzomib, doxorubicin, or melphalan, synergistically induced apoptosis in MM cells in vitro, in vivo and ex vivo without affecting non-myeloma cells. In early clinical trials, the oral, brain penetrating XPO1 inhibitor selinexor showed clear anti-myeloma activity however adverse events have been recorded, including nausea and anorexia. Our purpose was to investigate the use of oral KPT-8602, a novel small-molecule inhibitor of XPO1 with minimal brain penetration, which has been shown to have reduced toxicities in rodents and primates while maintaining potent anti-tumor effects. Experimental Procedures To test the efficacy of KPT-8602, we treated human MM cell lines (both parental and drug-resistant) with KPT-8602 ± currently used MM drugs, including bortezomib, carfilzomib, dexamethasone, doxorubicin, lenalidomide, melphalan, topotecan, and VP-16. Human MM cell lines assayed included RPMI-8226 (8226), NCI-H929 (H929), U266, and MM1.S, PI-resistant 8226-B25 and U266-PSR, doxorubicin-resistant 8226-Dox6 and 8226-Dox40, and melphalan-resistant 8226-LR5 and U266-LR6 cell lines. MM cells (2-4x106 cells/mL) were treated for 24 hours with KPT-8602 (300 nM), followed by treatment with one of the listed anti-MM agents for an additional 24 hours. MM cells were then assayed for cell viability (CellTiter-Blue, Promega). In addition, cells were treated with KPT-8602 ± anti-MM agents concurrently for 20 hours and assayed for apoptosis by flow cytometry. In vivo testing was done in NOD/SCID-g mice by intradermal injection of U266 MM cells. Treatment started 2 weeks after tumor challenge with KPT-8602 (10 mg/kg) ± melphalan (1 or 3 mg/kg) 2X/week (Tuesday, Friday) or with KPT-8602 alone 5X weekly (10 mg/kg) (Monday-Friday). A parallel experiment was run using the clinical XPO1 inhibitor KPT-330 (selinexor). Ex vivo testing was performed on MM cells from newly diagnosed/relapsed patient bone marrow aspirates with KPT-8602 ± bortezomib, carfilzomib, dexamethasone, doxorubicin, lenalidomide, melphalan, topotecan, or VP16. CD138+/light-chain+ cells were assayed for apoptosis by flow cytometry. Results Viability assay showed that KPT-8602 had low IC50values (~140 nM) as a single agent and functioned synergistically with bortezomib, carfilzomib, doxorubicin, melphalan, topotecan, and VP16. (CI values < 1.0). This synergistic effect was less pronounced in myeloma cells when KPT-8602 was used in combination with dexamethasone or lenalidomide. KPT-8602 ± bortezomib, carfilzomib, doxorubicin, melphalan, topotecan, and VP16 combination therapy also induced apoptosis in all MM cell lines tested, including drug-resistant cell lines, as shown by caspase 3 cleavage and flow cytometric analyses. NOD/SCID-gamma mouse tumor growth was reduced and survival increased in KPT-8602/melphalan-treated mice when compared to single-agent controls. In addition, mice treated with KPT-8602 5X weekly had significantly reduced tumor growth and increased survival when compared to 2X weekly drug administration. No toxicity was observed in KPT-8602-treated mice as determined by weight loss in both the 2X and 5X groups. In patient bone marrow biopsies, the combination of KPT-8602 ± bortezomib, carfilzomib, doxorubicin, melphalan, topotecan, and VP16 was more effective than single agents at inducing apoptosis in CD138+/LC+ MM cells in both newly diagnosed and relapsed/refractory patient samples. Conclusions We found that the novel XPO1 inhibitor KPT-8602 sensitizes MM cells to bortezomib, carfilzomib, doxorubicin, melphalan, topotecan, and VP16 as shown by apoptosis in parental and drug-resistant cell lines and by cell viability assays. Sensitization was found to be synergistic. In addition, KPT-8602 was effective in treatment of human MM tumors in mice as a single agent or in combination with melphalan and was effective when combined with several MM drugs in MM cell lines and MM patient bone marrow aspirates. KPT-8602 may be a potential candidate for future clinical trials. Disclosures Shacham: Karyopharm: Employment, Equity Ownership. Senapedis:Karyopharm Therapeutics, Inc.: Employment, Patents & Royalties.

P-gp localization in mitochondria and its functional characterization in multiple drug-resistant cell lines

2006 ◽  
Vol 312 (20) ◽  
pp. 4070-4078 ◽  
Author(s):  
Michela Solazzo ◽  
Ornella Fantappiè ◽  
Nadia Lasagna ◽  
Chiara Sassoli ◽  
Daniele Nosi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Functional Characterization ◽  
Resistant Cell ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Multiple Drug Resistant ◽  
Drug Resistant Cell
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