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Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer

Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an “old” antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, it...

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Autores principales: Lin, Chi-Kang, Bai, Meng-Yi, Hu, Teh-Min, Wang, Yu-Chi, Chao, Tai-Kuang, Weng, Shao-Ju, Huang, Rui-Lan, Su, Po-Hsuan, Lai, Hung-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891020/
https://www.ncbi.nlm.nih.gov/pubmed/26848771
http://dx.doi.org/10.18632/oncotarget.7113
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author Lin, Chi-Kang
Bai, Meng-Yi
Hu, Teh-Min
Wang, Yu-Chi
Chao, Tai-Kuang
Weng, Shao-Ju
Huang, Rui-Lan
Su, Po-Hsuan
Lai, Hung-Cheng
author_facet Lin, Chi-Kang
Bai, Meng-Yi
Hu, Teh-Min
Wang, Yu-Chi
Chao, Tai-Kuang
Weng, Shao-Ju
Huang, Rui-Lan
Su, Po-Hsuan
Lai, Hung-Cheng
author_sort Lin, Chi-Kang
collection PubMed
description Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an “old” antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. Nano-NI effectively inhibited the growth of ovarian cancer cells in which it induced a metabolic shift to glycolysis at a concentration of less than 3 μM in vitro and suppressed tumor growth without obvious toxicity at an oral dose of 100 mg/kg in vivo. In a pharmacokinetic study after oral administration, nano-NI showed rapid absorption (reaching the maximum plasma concentration within 5 min) and improved the bioavailability (the estimated bioavailability for oral nano-NI was 25%). In conclusion, nano-NI has the potential to be a new treatment modality for ovarian cancer and, therefore, further clinical trials are warranted.
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spelling pubmed-48910202016-06-20 Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer Lin, Chi-Kang Bai, Meng-Yi Hu, Teh-Min Wang, Yu-Chi Chao, Tai-Kuang Weng, Shao-Ju Huang, Rui-Lan Su, Po-Hsuan Lai, Hung-Cheng Oncotarget Research Paper Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an “old” antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. Nano-NI effectively inhibited the growth of ovarian cancer cells in which it induced a metabolic shift to glycolysis at a concentration of less than 3 μM in vitro and suppressed tumor growth without obvious toxicity at an oral dose of 100 mg/kg in vivo. In a pharmacokinetic study after oral administration, nano-NI showed rapid absorption (reaching the maximum plasma concentration within 5 min) and improved the bioavailability (the estimated bioavailability for oral nano-NI was 25%). In conclusion, nano-NI has the potential to be a new treatment modality for ovarian cancer and, therefore, further clinical trials are warranted. Impact Journals LLC 2016-02-01 /pmc/articles/PMC4891020/ /pubmed/26848771 http://dx.doi.org/10.18632/oncotarget.7113 Text en Copyright: © 2016 Lin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lin, Chi-Kang
Bai, Meng-Yi
Hu, Teh-Min
Wang, Yu-Chi
Chao, Tai-Kuang
Weng, Shao-Ju
Huang, Rui-Lan
Su, Po-Hsuan
Lai, Hung-Cheng
Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title_full Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title_fullStr Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title_full_unstemmed Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title_short Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
title_sort preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891020/
https://www.ncbi.nlm.nih.gov/pubmed/26848771
http://dx.doi.org/10.18632/oncotarget.7113
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