title: Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer.
abstract: 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.
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan.
authors: Chi-Kang
authors: CK
authors: Lin
authors: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors: Meng-Yi
authors: MY
authors: Bai
authors: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors: Teh-Min
authors: TM
authors: Hu
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan.
authors: Yu-Chi
authors: YC
authors: Wang
authors: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Tai-Kuang
authors: TK
authors: Chao
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors: Shao-Ju
authors: SJ
authors: Weng
authors: Department of Obstetrics and Gynecology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Rui-Lan
authors: RL
authors: Huang
authors: Department of Obstetrics and Gynecology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Po-Hsuan
authors: PH
authors: Su
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Hung-Cheng
authors: HC
authors: Lai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009534:Niclosamide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013535:Suspensions; D009534:Niclosamide
keywords: cancer metabolism; nanoformulation; nanomedicine; niclosamide; ovarian cancer