Copper oxide nanoparticles inhibit pancreatic tumor growth primarily by targeting tumor initiating cells
Autor: | Yuval Shaked, Iris S. Weitz, Ziv Raviv, Dvir Shechter, Michael Timaner, Haim Azhari, Or Perlman, Madeleine Benguigui, Sarit Sivan, Tal Kan |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cell death Cancer therapy Cell Survival Population lcsh:Medicine Metal Nanoparticles Antineoplastic Agents Apoptosis Article Metastasis 03 medical and health sciences Mice 0302 clinical medicine Pancreatic tumor Cancer stem cell Pancreatic cancer Cell Line Tumor mental disorders medicine Cytotoxic T cell Animals Humans Viability assay education lcsh:Science Cell Proliferation Membrane Potential Mitochondrial education.field_of_study Multidisciplinary Chemistry lcsh:R medicine.disease Pancreatic Neoplasms 030104 developmental biology Cancer research Neoplastic Stem Cells Heterografts Nanoparticles lcsh:Q Reactive Oxygen Species 030217 neurology & neurosurgery Copper |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
ISSN: | 2045-2322 |
Popis: | Cancer stem cells, also termed tumor initiating cells (TICs), are a rare population of cells within the tumor mass which initiate tumor growth and metastasis. In pancreatic cancer, TICs significantly contribute to tumor re-growth after therapy, due to their intrinsic resistance. Here we demonstrate that copper oxide nanoparticles (CuO-NPs) are cytotoxic against TIC-enriched PANC1 human pancreatic cancer cell cultures. Specifically, treatment with CuO-NPs decreases cell viability and increases apoptosis in TIC-enriched PANC1 cultures to a greater extent than in standard PANC1 cultures. These effects are associated with increased reactive oxygen species (ROS) levels, and reduced mitochondrial membrane potential. Furthermore, we demonstrate that CuO-NPs inhibit tumor growth in a pancreatic tumor model in mice. Tumors from mice treated with CuO-NPs contain a significantly higher number of apoptotic TICs in comparison to tumors from untreated mice, confirming that CuO-NPs target TICs in vivo. Overall, our findings highlight the potential of using CuO-NPs as a new therapeutic modality for pancreatic cancer. |
Databáze: | OpenAIRE |
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