Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
| العنوان: | Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating |
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| المؤلفون: | Petr Stepka, Jaromír Gumulec, Michal Masarik, René Kizek, Aneta Krizova, Vojtech Adam, Martina Raudenská, Petr Babula, Jan Balvan |
| المصدر: | PLOS ONE. 2015, vol. 10, issue 12, p. 1-23. PLoS ONE PLoS ONE, Vol 10, Iss 12, p e0145016 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Homeobox protein NANOG, Entosis, Cell Survival, Cell, Population, lcsh:Medicine, Cell Communication, holografická mikroskopie, Biology, Endoplasmic Reticulum, Time-Lapse Imaging, Inhibitory Concentration 50, holographic microscopy, SOX2, Cell Line, Tumor, Mitophagy, Autophagy, medicine, Humans, Cell Self Renewal, Neoplasm Metastasis, lcsh:Science, education, Cell Size, Principal Component Analysis, education.field_of_study, Multidisciplinary, Oxidativní stres, rakovina prostaty, Gene Expression Profiling, lcsh:R, Prostatic Neoplasms, Flow Cytometry, prostate cancer, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, Oxidative Stress, medicine.anatomical_structure, Oxidative stress, Cancer cell, lcsh:Q, Reactive Oxygen Species, Research Article, Naphthoquinones |
| الوصف: | Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate. Fenotyp rezistentní rakoviny představuje hlavní překážku v úspěšné léčbě rakoviny prostaty. Primárním cílem naší studie bylo prozkoumat mechanismy rezistence v pokročilém druhu rakovinných buněk prostaty (PC-3) a objasnit roli autofagie v tomto procesu. |
| وصف الملف: | text; application/pdf |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91516a47431ad577ecde061274511d61 https://doi.org/10.1371/journal.pone.0145016 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....91516a47431ad577ecde061274511d61 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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