The antihelminthic drug niclosamide effectively inhibits the malignant phenotypes of uveal melanoma in vitro and in vivo

Theranostics
Jingfeng ZhouJingxuan Pan

Abstract

Uveal melanoma (UM) is a lethal intraocular malignancy with an average survival of only 2~8 months in patients with hepatic metastasis. Currently, there is no effective therapy for metastatic UM. Here, we reported that niclosamide, an effective repellence of tapeworm that has been approved for use in patients for approximately 50 years, exhibited strong antitumor activity in UM cells in vitro and in vivo. We showed that niclosamide potently inhibited UM cell proliferation, induced apoptosis and reduced migration and invasion. p-Niclosamide, a water-soluble niclosamide, exerted potent in vivo antitumor activity in a UM xenograft mouse model. Mechanistically, niclosamide abrogated the activation of the NF-κB pathway induced by tumor necrosis factor α (TNFα) in UM cells, while niclosamide elevated the levels of intracellullar and mitochondrial reactive oxygen species (ROS) in UM cells. Quenching ROS by N-acetylcysteine (NAC) weakened the ability of niclosamide-mediated apoptosis. Matrix metalloproteinase 9 (MMP-9) knockdown by shRNA potentiated, while ectopic expression of MMP-9 rescued, the niclosamide-attenuated invasion, implying that MMP-9 is pivotal for invasion blockage by niclosamide in UM cells. Furthermore, our results sh...Continue Reading

Citations

Nov 14, 2019·Current Pharmaceutical Design·Morteza GhandadiSorour Ashari
Dec 28, 2019·Pigment Cell & Melanoma Research·Jackson R RichardsShannon J Odelberg
Mar 5, 2020·Molecular Cancer·Bei JinJingxuan Pan
Mar 28, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Yisong XuPenggao Dai
Jan 20, 2019·Current Topics in Medicinal Chemistry·Kamakshi DanduCh Mohan Rao
Dec 21, 2018·Molecular Medicine Reports·Qiong Yi, Wen-Jin Zou
May 16, 2020·International Journal of Molecular Sciences·Tereza KauerováPeter Kollar
Mar 10, 2020·Pigment Cell & Melanoma Research·Lucia González-RuizPablo Ramos-García
Oct 27, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jingfeng ZhouJingxuan Pan
Nov 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·So-Yeon ParkJeong-Seok Nam
Dec 14, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yanli JinJingxuan Pan
Dec 5, 2020·OncoTargets and Therapy·Yu Ning ChenWen Bin Wei
Jun 18, 2021·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Seyed Ebrahim Alavi, Hasan Ebrahimi Shahmabadi

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Methods Mentioned

BETA
flow cytometry
ELISA
xenografts
nuclear translocation
xenograft

Software Mentioned

GraphPad Prism

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