類黃酮WYC0209經由針對CD133作為尿路上皮癌細胞抗癌幹性的有效佐劑
葉碧雯1,2,8、尤亮恩1,2、李經家1,2、楊顓丞3、李威明1,2,4、吳永昌3、韋又菁5
、李學德6、孔美蘭7*、吳文正1,2,8,9*
高雄醫學大學 泌尿學科1，高雄醫學大學附設醫院 泌尿科2，高雄醫學大學天然藥物研究所3，衛福部屏東醫院 泌尿科4，高雄市立大同醫院 病理科5，國立陽明醫學大學 解剖與細胞生物學研究所6，高雄榮民總醫院醫學教育與研究科7，高雄醫學大學 再生醫學與細胞治療中心8，國立中山大學醫學科學技術研究所9
The protoapigenone analogue WYC0209 targeted CD133 as a potent adjuvant agent for anti-cancer stemness in urothelial cancer cells
Bi-Wen Yeh1,2,8, Liang-En Yu1,2, Ching-Chia Li1,2,, Juan-Cheng Yang3, Wei-Ming Li1,2,4, Yang-Chang Wu3, Yu-Ching Wei5, Hsueh-Te Lee6, Mei-Lang Kung7 * and Wen-Jeng Wu1,2,8,9 *
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung1; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung2; Graduate institute of natural products, Kaohsiung Medical University, Kaohsiung; Department of Urology3, Ministry of Health and Welfare Pingtung Hospital, Pingtung4; Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung5; Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei6; Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung7; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung8; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan9
Purposes： The unresectable lesions of urothelial carcinoma (UC) that are resistant to therapeutic interventions are the major cause leading to death. Previous studies had shown that the resistance and metastatic consequence may arise from cancer stem-like cells population. The phytochemical flavonoids have promised bioactivity and potent anti-carcinogenic effects, and trap great attentions for cancer chemoprevention and/or adjuvant chemotherapy. However, the mechanisms of flavonoids on cancer stemness are still obscured.
Materials and Methods: In the present study, we analyzed the biofunctional effects of as-prepared flavonoid derivative-WYC0209 on T24, BFTC 905 and BFTC909 human UC cell lines.
Results: Our results demonstrated that WYC0209 significantly induced anti-cell viability on UC cells through decreased Akt/NFkB signaling. Moreover, WYC0209 enhanced the cell apoptosis through activated the caspase-3 activity and inactivated Bcl-xL expression. Interestingly, WYC0209 dramatically inhibited the cancer stem cells (CSCs) traits, including attenuation of side population and tumorsphere formation in which were through declined EMT-CSCs markers including MDR1, ABCG2 and BMI-1. We further validated the effects of WYC0209 on several CSC surface markers including CD133, CD44, SOX-2 and Nanog. The results showed that WYC0209 markedly inhibited CD133 expressions in both transcriptional and translational levels. High expression level of CD133 was also demonstrated in human upper tract UC specimens.
Conclusions: WYC0209 may potentially acts as an adjuvant agent to against CD133-driven UC CSCs and provide a beneficial strategy to against UC cancer therapeutics resistant.