Copper oxide nanoparticles inhibit pancreatic tumor growth primarily by targeting tumor initiating cells

• Published in: Scientific reports Vol. 9; no. 1; pp. 12613 - 10
• Main Authors: Benguigui, Madeleine, Weitz, Iris S., Timaner, Michael, Kan, Tal, Shechter, Dvir, Perlman, Or, Sivan, Sarit, Raviv, Ziv, Azhari, Haim, Shaked, Yuval
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2019; Nature Publishing Group
• Subjects: 13/106; 13/51; 14/19; 14/34; 14/63; 631/67/1059; 631/80/82; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Copper; Copper - chemistry; Copper - pharmacology; Cytotoxicity; Heterografts; Humanities and Social Sciences; Humans; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Metal Nanoparticles; Metastases; Mice; Mitochondria; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Neoplastic Stem Cells - drug effects; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48959-8

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.