دورية أكاديمية
Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram
| العنوان: | Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram |
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| المؤلفون: | Ting Sun, Wei Yang, Sneh M. Toprani, Wei Guo, Lile He, Albert B. DeLeo, Soldano Ferrone, Gong Zhang, Enwen Wang, Zunwen Lin, Pan Hu, Xinhui Wang |
| المصدر: | Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-14 (2020) |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Breast cancer, Stem cells, Immunogenic cell death, Radiation, Disulfiram, Copper, Medicine, Cytology, QH573-671 |
| الوصف: | Abstract Background The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response. Methods High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24−/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA). Results We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors. Conclusion DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis. Graphical abstract |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| Relation: | http://link.springer.com/article/10.1186/s12964-019-0507-3; https://doaj.org/toc/1478-811X |
| DOI: | 10.1186/s12964-019-0507-3 |
| URL الوصول: | https://doaj.org/article/aa6db65e6fa94485b6ba2a5b8b7affce |
| رقم الأكسشن: | edsdoj.6db65e6fa94485b6ba2a5b8b7affce |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-019-0507-3 |