A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

Abstract

The incidence and mortality rate of urological cancers is increasing yearly. Niclosamide has been repurposed as an anti‐cancer drug in recent years. Synthesized derivative of niclosamide was testified for its anti‐cancer activity in urological cancers. MTT assay was used to measure the cytotoxicity effect of niclosamide and its derivatives in urological cancer cell lines. Migratory ability was monitored by scratch migration assay. Apoptosis and cell cycle changes were analyzed by annexin V and PI staining. The apoptosis‐related signal proteins were evaluated by western blotting. T24 had the best drug sensitivity with the lowest IC 50 in niclosamide and B17 treatment than DU145 and Caki‐1 cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but apoptotic bodies and morphology changes were not prominent in T24, Caki‐1, and DU145 cells. The migratory ability was inhibited in niclosamide treatment than control group on Caki‐1 cells and niclosamide and B17 treatment than control group on DU145 cells. Early apoptosis cells were increased after niclosamide and B17 treatment than control group without cell cycle changes in T24, Caki‐1, and DU145 cells. Programmed cell death was activated majorly through PAPR and bcl‐2 in T24 and caspase‐3 in Caki‐1 cells, respectively. Niclosamide and B17 derivative had good ability in inhibition proliferation and migratory ability in T24, Caki‐1, and DU145 cells without prominent morphology and apoptotic body changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early apoptosis was induced after niclosamide and B17 treatment through different mechanisms in T24, Caki‐1, and DU145 cells.

Ring-Substituted 1-Hydroxynaphthalene-2-Carboxanilides Inhibit Proliferation and Trigger Mitochondria-Mediated Apoptosis

“…Multiple studies showed the preparation of niclosamide's derivatives by replacing the nitro group with another convenient substituent in order to improve its anticancer activity and also to overcome its physicochemical limitations. Consistent with our results, the introduction of another electron-withdrawing substituent -CF 3 on the anilide part of the molecule was found to be favorable [52][53][54].…”

Establishment of amygdalin antitumor efficacy against human acute monocytic leukemia cell line (THP‐1) with antimicrobial investigations, in vitro Study

“…Vit b 17 induced apoptosis in THP-1 cells by up-regulating the expression of BAX and down-regulating the expression of BCL2 these ndings are similar to that reported via (Liczbiński & Bukowska, 2018) . This suggests that vitamin B17 has pro-apoptotic effects on THP-1 cells (Wu et al, 2018) .…”

The magic bullet: Niclosamide

“…Clinically, the major challenge for niclosamide is poor oral bioavailability, potentially limiting its use as a cancer drug ( 11 , 156 ). Efforts have been taken to improved its bioavailability, including: (1) reformulating niclosamide for better delivery and stability ( 158 , 163 – 166 ) and (2) modifying the structure of niclosamide to generate derivatives with enhanced efficiency ( 167 , 168 ) or pharmacokinetics ( 169 , 170 ). Nonetheless, the process of identifying these derivatives involved screens with readouts of either cell apoptosis or oncogenic pathway inhibition, processes that may not reflect the primary property of niclosamide as anti-tumor compound, thereby reinforcing the need to identify the primary target of niclosamide to accelerate pharmacological development of new derivatives.…”