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

Madeleine Benguigui, Iris S. Weitz, Michael Timaner, Tal Kan, Dvir Shechter, Or Perlman, Sarit Sivan, Ziv Raviv, Haim Azhari, Yuval Shaked

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number12613
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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