MP01-09 LUTEOLIN SUPPRESSES SQUAMOUS DIFFERENTIATION OF BLADDER CANCER AND CANCER GROWTH VIA REGULATION OF MAMMALIAN TARGET OF RAPAMYCIN PATHWAY

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-09 LUTEOLIN SUPPRESSES SQUAMOUS DIFFERENTIATION OF BLADDER CANCER AND CANCER GROWTH VIA REGULATION OF MAMMALIAN TARGET OF RAPAMYCIN PATHWAY Keitaro Iida*, Taku Naiki, Aya Naiki-Ito, Takashi Nagai, Satoshi Nozaki, Toshiki Etani, Ryosuke Ando, Noriyasu Kawai, and Takahiro Yasui Keitaro Iida*Keitaro Iida* More articles by this author , Taku NaikiTaku Naiki More articles by this author , Aya Naiki-ItoAya Naiki-Ito More articles by this author , Takashi NagaiTakashi Nagai More articles by this author , Satoshi NozakiSatoshi Nozaki More articles by this author , Toshiki EtaniToshiki Etani More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Noriyasu KawaiNoriyasu Kawai More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Luteolin is a natural flavonoid with strong antioxidative properties. The anti-cancer effect of luteolin in several cancers has been reported; however, little is known about its effect on bladder cancer. Here, we explored the effects of luteolin on bladder cancer. METHODS: Human urothelial carcinoma cell lines, T24 and 5637, were used. A WST-8 assay and western blotting were used to evaluate cell viability and protein signaling, respectively. Thioredoxin activity and reactive oxygen species (ROS) production were evaluated using thioredoxin and dichlorodihydrofluorescein diacetate assays, respectively. Furthermore, we examined the impact of a 20-week luteolin-rich diet on the growth of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)–induced bladder cancer in a rat model (luteolin concentrations were control, 20 ppm and 100 ppm; n=20, respectively). RESULTS: Luteolin induced a dose-dependent reduction in the number of viable cells; it also increased thioredoxin activity and decreased ROS production. Luteolin downregulated phospho-p70S6K and phospho-S6K (pS6), substrates of mammalian target of rapamycin (mTOR), which was reversed by the thioredoxin inhibitor, PX-12. This indicates luteolin inhibited the mTOR pathway by regulating thioredoxin and ROS. In an in vivo study, BBN-induced rat bladder cancer was inhibited by the oral administration of luteolin; the Ki67 labeling index and pS6 expression were also decreased. Further, both plasma and urine luteolin-3'-O-glucuronide concentrations were strongly associated with the Ki67 labeling index (r=0.31, -0.41, respectively) and the pS6 expression (r=-0.60, -0.62, respectively). Moreover, a significant decrease in the squamous differentiation of bladder cancer was attributed to plasma luteolin-3'-O-glucuronide concentrations (p<0.01). CONCLUSIONS: Luteolin may represent another natural product–derived therapeutic agent that acts against bladder cancer by up-regulating thioredoxin activity and inhibiting mTOR signaling. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e5-e5 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keitaro Iida* More articles by this author Taku Naiki More articles by this author Aya Naiki-Ito More articles by this author Takashi Nagai More articles by this author Satoshi Nozaki More articles by this author Toshiki Etani More articles by this author Ryosuke Ando More articles by this author Noriyasu Kawai More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...