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Int J Nanomedicine. 2017 Apr 5;12:2553-2567. doi: 10.2147/IJN.S130753. eCollection 2017.

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

Author information

1
Department of Cell Biology, Second Military Medical University.
2
State 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.
3
Department of Urinary Surgery.
4
Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Abstract

Recent studies have shown that metal and metal oxide have a potential function in antitumor 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:

A375 cell line; CONPs; MITF; SOX10; WM266-4 cell line; cancer stem cells; clathrin-mediated endo cytosis; cuprous oxide nanoparticles; melanoma

PMID:
28435246
PMCID:
PMC5388199
DOI:
10.2147/IJN.S130753
[Indexed for MEDLINE]
Free PMC Article

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