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Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells

Authors Yu B, Wang Y, Yu XL, Zhang H, Zhu J, Wang C, Chen F, Liu C, Wang J, Zhu H

Received 20 December 2016

Accepted for publication 28 February 2017

Published 5 April 2017 Volume 2017:12 Pages 2553—2567

DOI https://doi.org/10.2147/IJN.S130753

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Bin Yu,1,2,* Ye Wang,3,* Xinlu Yu,1,* Hongxia Zhang,1 Ji Zhu,4 Chen Wang,1 Fei Chen,1 Changcheng Liu,1 Jingqiang Wang,2 Haiying Zhu1

1Department of Cell Biology, Second Military Medical University, 2State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics and Development, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Genetics and Development, School of Life Sciences, Fudan University, 3Department of Urinary Surgery, 4Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: Recent studies have shown that metal and metal oxide have a potential function in anti-tumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271+/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271+/high cells could accumulate more CONPs than CD271-/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD271, SOX10 and MITF. These results above proved the effectiveness of CONPs in inhibiting melanoma progress through multiple pathways, especially through targeting melanoma stem cells.

Keywords: cuprous oxide nanoparticles, CONPs, melanoma, cancer stem cells, A375 cell line, WM266-4 cell line, MITF, SOX10, clathrin-mediated endo­cytosis

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