Academic Journal
Activation of lysosomal mediated cell death in the course of autophagy by mTORC1 inhibitor
| العنوان: | Activation of lysosomal mediated cell death in the course of autophagy by mTORC1 inhibitor |
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| المؤلفون: | Sameer Ullah Khan, Anup Singh Pathania, Abubakar Wani, Kaneez Fatima, Mubashir Javed Mintoo, Baseerat Hamza, Masroor Ahmad Paddar, Wadhwa Bhumika, Loveleena Kour Anand, Mir Shahid Maqbool, Sameer Ahmad Mir, Jaspreet Kour, Vunnam Venkateswarlu, Dilip Manikrao Mondhe, Sanghapal D. Sawant, Fayaz Malik |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-13 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Lysosomal biogenesis plays a vital role in cell fate. Under certain conditions, excessive lysosomal biogenesis leads to susceptibility for lysosomal membrane permeabilization resulting in various pathological conditions including cell death. In cancer cells apoptosis machinery becomes dysregulated during the course of treatment, thus allows cancer cells to escape apoptosis. So it is therefore imperative to identify cytotoxic agents that exploit non-apoptotic mechanisms of cell death. Our study showed that pancreatic cancer cells treated with SDS-203 triggered an incomplete autophagic response and a nuclear translocation of transcriptional factor TFEB. This resulted in abundant biosynthesis and accumulation of autophagosomes and lysosomes into the cells leading to their death. It was observed that the silencing of autophagy genes didn’t alter the cell fate, whereas siRNA-mediated silencing of TFEB subdued SDS-203 mediated lysosomal biogenesis and associated cell death. Further mouse tumors treated with SDS-203 showed a significant reduction in tumor burden and increased expression of lysosomal markers. Taken together this study demonstrates that SDS-203 treatment triggers non-apoptotic cell death in pancreatic cancer cells through a mechanism of lysosome over accumulation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-022-07955-1 |
| URL الوصول: | https://doaj.org/article/4068e835a7fa4caf83866b11c58f2661 |
| رقم الانضمام: | edsdoj.4068e835a7fa4caf83866b11c58f2661 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-022-07955-1 |