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

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 Devel...

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Autores principales: Yu B, Wang Y, Yu XL, Zhang H, Zhu J, Wang C, Chen F, Liu C, Wang J, Zhu H
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:cf4631aef0b24331bac1536fc5ab252b2021-12-02T03:10:57ZCuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells1178-2013https://doaj.org/article/cf4631aef0b24331bac1536fc5ab252b2017-04-01T00:00:00Zhttps://www.dovepress.com/cuprous-oxide-nanoparticle-inhibited-melanoma-progress-by-targeting-me-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bin 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 endo­cytosisYu BWang YYu XLZhang HZhu JWang CChen FLiu CWang JZhu HDove Medical PressarticleMelanomaCuprous Oxide Nanoparticles (CONPs)CD271Cancer stem cellsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2553-2567 (2017)
institution DOAJ
collection DOAJ
language EN
topic Melanoma
Cuprous Oxide Nanoparticles (CONPs)
CD271
Cancer stem cells
Medicine (General)
R5-920
spellingShingle Melanoma
Cuprous Oxide Nanoparticles (CONPs)
CD271
Cancer stem cells
Medicine (General)
R5-920
Yu B
Wang Y
Yu XL
Zhang H
Zhu J
Wang C
Chen F
Liu C
Wang J
Zhu H
Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
description 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
format article
author Yu B
Wang Y
Yu XL
Zhang H
Zhu J
Wang C
Chen F
Liu C
Wang J
Zhu H
author_facet Yu B
Wang Y
Yu XL
Zhang H
Zhu J
Wang C
Chen F
Liu C
Wang J
Zhu H
author_sort Yu B
title Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
title_short Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
title_full Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
title_fullStr Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
title_full_unstemmed Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
title_sort cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/cf4631aef0b24331bac1536fc5ab252b
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