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.
Highlights
Funding informationCheng Hsin General Hospital Foundation, Grant/Award Number: CH-NDMC-105-7 and CH-NDMC-106-6; Tri-Service General Hospital, Grant/Award Number: TSGH-C105-051 and TSGH-C106-045; Ministry of Science and Technology, Taiwan, Grant/Award Number: MOST 104-2314-B-016-040-MY3; National Defense Medical Center, Grant/Award Number: MAB-106-074
Cancer is the pioneer of ten death causes in Taiwan, 92,682 people were first diagnosed with invasive cancer accompanied 42,559 people death in 2011.1 7932 people was belonged to urological cancers, about 8.6% of total invasive cancer accompanied 2408 people deaths (30.4% mortality rate).[1]
Urothelial carcinoma, renal cell carcinoma, and prostatic carcinoma are three prevalent tumors worldwide. Despite conventional therapies such as surgery, radiation, and chemotherapy, the overall survival rate for these cancers still need improving target therapy and immunotherapy are emerging as new therapies with increasing survival in urothelial carcinoma and renal cell carcinoma.[19,20,21]
Summary
Cheng Hsin General Hospital Foundation, Grant/Award Number: CH-NDMC-105-7 and CH-NDMC-106-6; Tri-Service General Hospital, Grant/Award Number: TSGH-C105-051 and TSGH-C106-045; Ministry of Science and Technology, Taiwan, Grant/Award Number: MOST 104-2314-B-016-040-MY3; National Defense Medical Center, Grant/Award Number: MAB-106-074
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