دورية أكاديمية
Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs
| العنوان: | Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs |
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| المؤلفون: | Nalli, Ancy D., Brown, Lauren E., Thomas, Cheryl L., Sayers, Thomas J., Porco, John A., Henrich, Curtis J. |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | Boston University: OpenBU |
| مصطلحات موضوعية: | Science & technology, Multidisciplinary sciences, Ubiquitin ligase itch, Cancer-cells, C-flip, Resistance, Inhibition, Activation, Derivatives, Death, Chemotherapy, Flavaglines |
| الوصف: | Rocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells. Rocaglamide alone induced cell cycle arrest, but not apoptosis. Rocaglates averaged 4–5-fold higher potency as TRAIL sensitizers than as protein synthesis inhibitors suggesting a potential window for maximizing TRAIL sensitization while minimizing effects of general protein synthesis inhibition. A wide range of other rocaglate effects (e.g. on JNK or RAF-MEK-ERK signaling, death receptor levels, ROS, ER stress, eIF4E phosphorylation) were assessed, but did not contribute to TRAIL sensitization. Other than a rapid loss of MCL-1, rocaglates had minimal effects on mitochondrial apoptotic pathway proteins. The identification of structurally diverse/mechanistically similar TRAIL sensitizing rocaglates provides insights into both rocaglate structure and function and potential further development for use in RCC-directed combination therapy. ; This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of NIH, Frederick. National Lab, Center for Cancer Research. Research performed at ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 11 p. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | Scientific Reports; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000451748700041&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654Test; Ancy D. Nalli, Lauren E. Brown, Cheryl L. Thomas, Thomas J. Sayers, John A. Porco, Curtis J. Henrich. 2018. "Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs." SCIENTIFIC REPORTS, Volume 8, pp. ? - ? (11). https://doi.org/10.1038/s41598-018-35908-0Test; https://hdl.handle.net/2144/33279Test |
| DOI: | 10.1038/s41598-018-35908-0 |
| الإتاحة: | https://doi.org/10.1038/s41598-018-35908-0Test https://hdl.handle.net/2144/33279Test http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000451748700041&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.1121C43F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-018-35908-0 |