PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer |
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Authors: | Wen-Jung Chen Wen-Wei Sung Chia-Ying Yu Yu-Ze Luan Ya-Chuan Chang Sung-Lang Chen Tsung-Hsien Lee |
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Institution: | 1.Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (W.-J.C.); (W.-W.S.);2.School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (C.-Y.Y.); (Y.-Z.L.); (Y.-C.C.);3.Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan;4.Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan;5.Division of Infertility Clinic, Lee Women’s Hospital, Taichung 40201, Taiwan |
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Abstract: | Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to inhibit this pathway has identified a small molecule, PNU-74654, as an inhibitor of the β-catenin/TCF4 interaction. We evaluated the therapeutic role of PNU-74654 in two TC cell lines, NCCIT and NTERA2, by measuring cell viability, cell cycle transition and cell death. Potential pathways were evaluated by protein arrays and Western blots. PNU-74654 decreased cell viability and induced apoptosis of TC cells, with significant increases in the sub G1, Hoechst-stained, Annexin V-PI-positive rates. PNU-74654 treatment of both TC cell lines inhibited the TNFR1/IKB alpha/p65 pathway and the execution phase of apoptosis. Our findings demonstrate that PNU-74654 can induce apoptosis in TC cells through mechanisms involving the execution phase of apoptosis and inhibition of TNFR1/IKB alpha/p65 signaling. Therefore, small molecules such as PNU-74654 may identify potential new treatment strategies for TC. |
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Keywords: | PNU-74654 TNF receptor-1 apoptosis testicular cancer |
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