ANTI-TUMOR EFFECT OF NANAOMYCIN K, A COMPOUND EXTRACTED FROM STREPTOMYCES, ON PROSTATE CANCER CELL LINES IN VITRO AND IN VIVO

You have accessJournal of UrologyCME1 Apr 2023MP20-19 ANTI-TUMOR EFFECT OF NANAOMYCIN K, A COMPOUND EXTRACTED FROM STREPTOMYCES, ON PROSTATE CANCER CELL LINES IN VITRO AND IN VIVO Yuto Hirata, Katsumi Shigemura, Michika Moriwaki, Masato Iwatsuki, Tooru Ooya, Yuki Kan, Maeda Koki, Youngmin Yang, Takuji Nakashima, Hirotaka Matsuo, Jun Nakanishi, and Masato Fujisawa Yuto HirataYuto Hirata More articles by this author , Katsumi ShigemuraKatsumi Shigemura More articles by this author , Michika MoriwakiMichika Moriwaki More articles by this author , Masato IwatsukiMasato Iwatsuki More articles by this author , Tooru OoyaTooru Ooya More articles by this author , Yuki KanYuki Kan More articles by this author , Maeda KokiMaeda Koki More articles by this author , Youngmin YangYoungmin Yang More articles by this author , Takuji NakashimaTakuji Nakashima More articles by this author , Hirotaka MatsuoHirotaka Matsuo More articles by this author , Jun NakanishiJun Nakanishi More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003245.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nanaomycin K is a natural compound found in the cultured broth of “Streptomyces rosa subsp. notoensis” OS-3966 and has been reported to have an inhibitory effect on epithelial mesenchymal transition (EMT), an important mechanism of cancer cell invasion. In this study, we investigated the antitumor effect and EMT inhibitory effect of nanaomycin K on castration-resistant prostate cancer (CRPC) cell lines in vitro and in vivo. METHODS: Two human prostate cancer (PCa) cell lines, castration-dependent LNCaP and castration-independent PC-3, and one mice PCa cell line, castration-independent TRAMP-C2 were used. In vitro, TGF-β was added to PCa cell lines followed by treatment with nanaomycin K. Then the MTS assay was performed to examine cell proliferation. Also wound healing assay was conducted to evaluate cell migration. In addition, western blotting was conducted to investigate the expression of EMT markers and the MAPK pathway. In vivo, nanaomycin K was intratumorally administered to mice bearing TRAMP-C2 tumors, and tumor size and weight were observed over time. After removal, tumor immunohistochemistry (IHC) staining was conducted. RESULTS: Nanaomycin K significantly inhibited proliferation in all cell lines with or without TGF-β (p<0.001). Also, nanaomycin K also significantly inhibited the migration of TGF-β treated TRAMP-C2 (p=0.008) by wound healing.In western blotting, nanaomycin K decreased the expression of N-cadherin and Vimentin, indicating EMT progression, in all cell lines, and decreased the expression of Slug, which induces EMT, in LNCaP and TRAMP-C2. And regarding the MAPK signaling pathway, phospho-p38, phospho-SAPK/JNK and phospho-Erk1/2 were suppressed in LNCaP, while phospho-Erk1/2 was suppressed in both LNCaP and TRAMP-C2. The effect was more pronounced in TGF-β treated groups. Finally, in animal experience, nanaomycin K showed anti-tumor effects in vivo (0.5 or 1.0 mg/body nanaomycin K: p=0.001). Also, in IHC staining using mice tumor, phospho-Erk1/2 expression was significantly decreased by nanaomycin K (1.0 mg/body: p=0.031). And the expression of Cleaved-Caspase 3 was concentration dependently increased by nanaomycin K (0.5 mg/body: p=0.009, 1.0 mg/body: p<0.001). CONCLUSIONS: Nanaomycin K had anti-tumor effects and inhibited invasion by suppressing the expression of Slug, a protein that induces EMT and the phosphorylation of MAPK signaling pathway in prostate cancer. So nanaomycin K could be a therapeutic agent for CRPC due to EMT and MAPK inhibition. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e283 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yuto Hirata More articles by this author Katsumi Shigemura More articles by this author Michika Moriwaki More articles by this author Masato Iwatsuki More articles by this author Tooru Ooya More articles by this author Yuki Kan More articles by this author Maeda Koki More articles by this author Youngmin Yang More articles by this author Takuji Nakashima More articles by this author Hirotaka Matsuo More articles by this author Jun Nakanishi More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF downloadLoading ...