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.

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

“…We found that CONPs can selectively induce apoptosis of melanoma cells and have little hepatoxicity and renal toxicity. 15,16 As is commonly known, melanoma with a mutated BRAF V600E gene requires copper to activate the ERK1/2-mediated signaling pathway, which is important for the rapid proliferation of melanoma. 17,22,23 The high requirement of copper suggested that blocking copper may be a method that could be used for melanoma therapy.…”

“…Combining the azurite ore and nanoscience, our research group has examined the possibility of applying cuprous oxide nanoparticles (CONPs) to cancer therapy. 15,16 As CRPC is one of the possible manifestations of ADT during prostate cancer treatment and the overall survival benefit of marketed drugs is limited, it is necessary to explore the pharmacological effects of CONPs on CRPC. In addition, our previous study shows that melanoma is highly sensitive to CONPs 15,16 and that melanoma and prostate cancer exhibit similar copper metabolism disorder characteristics, [17][18][19] which suggests that CONPs may also affect prostate cancer, including CRPC.…”

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

“…12,13 Our current research tried to find the way by which CONPs entered into cells. To date, there are a few kinds of endocytosis uncovered, via which particles and macromolecules enter into cells, such as clathrin-mediated endocytosis, 29 macropinocytosis, 30 and clathrin-and caveola-independent endocytoses.…”

“…12,13 Briefly, adding 0.35 mL of 0.1 M CuSO 4 to 3 mL of 0.1 M cetyltrimethylammonium bromide in a test tube and allowing the solutions to mix for ~5 minutes. Then, adding 10 mL of fresh, chilled 0.04 M NaBH 4 to the mixture.…”

“…[8][9][10][11] As a new member of potential antitumor drugs, cuprous oxide nanoparticles (CONPs) have been proven not only to induce apoptosis of tumor cells selectively in vitro but also to inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. 12,13 In the meantime, a lot of studies focusing on the biological properties of melanoma provided more strategies for finding or designing new drugs and therapies.…”