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.

A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

“…Another study indicates that Niclosamide may also exert its anticancer activity through inhibition of Wnt/β-catenin target gene FGF1 in ovarian cancer [32]. More recently, efforts have been devoted to developing Niclosamide analogs with higher bioavailability [77] and/or designing more efficacious formulations for preclinical and eventually clinical studies [78].…”

CD133 Targeted PVP/PMMA Microparticle Incorporating Levamisole for the Treatment of Ovarian Cancer

“…We set up an electrospray (ES) system as described in our previous studies [25][26][27][28][29]. First, 0.078-2.5 mg LEVA was dissolved in 2 mL of cosolvent [acetone/dimethylformamide (Ace/DMF) = 1/2, v/v] through ultrasonication for 10 min to generate LEVA stock solution.…”

Repurposing of Anthelminthics as Anticancer Drugs

“…Signaling pathways Cancer cells [45], osteosarcoma [37], STAT3 CSCs [46], Wnt/β-catenin ovarian cancer [43], prostate cancer [36], NSCLC/ c-Jun-ROS [35], colorectal cancer/TNIK [30].…”

“…Transcription factors NFκB and ATF3 were targeted by niclosamide in hepatocellular carcinoma (HCC) and leukemia, respectively [36,38]. In ovarian cancer, the effects of the drug were related to the suppression of mitochondrial respiration [45].…”