title: Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria.
abstract: Metal and its oxide nanoparticles show ideal pharmacological activity, especially in anti-tumor therapy. Our previous study demonstrated that cuprous oxide nanoparticles (CONPs) selectively induce apoptosis of tumor cells in vitro. To explore the anti-tumor properties of CONPs in vivo, we used the particles to treat mouse subcutaneous melanoma and metastatic lung tumors, based on B16-F10 mouse melanoma cells, by intratumoral and systemic injections, respectively. The results showed that CONPs significantly reduced the growth of melanoma, inhibited the metastasis of B16-F10 cells and increased the survival rate of tumor-bearing mice. Importantly, the results also indicated that CONPs were rapidly cleared from the organs and that these particles exhibited little systemic toxicity. Furthermore, we observed that CONPs targeted the mitochondria, which resulted in the release of cytochrome C from the mitochondria and the activation of caspase-3 and caspase-9 after the CONPs entered the cells. In conclusion, CONPs can induce the apoptosis of cancer cells through a mitochondrion-mediated apoptosis pathway, which raises the possibility that CONPs could be used to cure melanoma and other cancers.
authors.affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, PR of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: H X
authors.initials: HX
authors.lastname: Zhang
authors.forename: X Y
authors.initials: XY
authors.lastname: Zi
authors.forename: X H
authors.initials: XH
authors.lastname: Pan
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: W D
authors.initials: WD
authors.lastname: Luo
authors.forename: J X
authors.initials: JX
authors.lastname: Li
authors.forename: H Y
authors.initials: HY
authors.lastname: Zhu
authors.forename: Y P
authors.initials: YP
authors.lastname: Hu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000494:pharmacology* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003300:Copper; C000520:cuprous oxide