Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo
Since castration-resistant prostate cancer (CRPC) acquires resistance to molecularly targeted drugs, discovering a class of drugs with different mechanisms of action is needed for more efficient treatment. In this study, we investigated the anti-tumor effects of nanaomycin K, derived from “<i>...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/10/2684 |
| _version_ | 1797600705013350400 |
|---|---|
| author | Yuto Hirata Katsumi Shigemura Michika Moriwaki Masato Iwatsuki Yuki Kan Tooru Ooya Koki Maeda Youngmin Yang Takuji Nakashima Hirotaka Matsuo Jun Nakanishi Masato Fujisawa |
| author_facet | Yuto Hirata Katsumi Shigemura Michika Moriwaki Masato Iwatsuki Yuki Kan Tooru Ooya Koki Maeda Youngmin Yang Takuji Nakashima Hirotaka Matsuo Jun Nakanishi Masato Fujisawa |
| author_sort | Yuto Hirata |
| collection | DOAJ |
| description | Since castration-resistant prostate cancer (CRPC) acquires resistance to molecularly targeted drugs, discovering a class of drugs with different mechanisms of action is needed for more efficient treatment. In this study, we investigated the anti-tumor effects of nanaomycin K, derived from “<i>Streptomyces rosa</i> subsp. <i>notoensis</i>” OS-3966. The cell lines used were LNCaP (non-CRPC), PC-3 (CRPC), and TRAMP-C2 (CRPC). Experiments included cell proliferation analysis, wound healing analysis, and Western blotting. In addition, nanaomycin K was administered intratumorally to TRAMP-C2 carcinoma-bearing mice to assess effects on tumor growth. Furthermore, immuno-histochemistry staining was performed on excised tissues. Nanaomycin K suppressed cell proliferation in all cell lines (<i>p</i> < 0.001) and suppressed wound healing in TRAMP-C2 (<i>p</i> = 0.008). Nanaomycin K suppressed or showed a tendency to suppress the expression of N-cadherin, Vimentin, Slug, and Ras in all cell lines, and suppressed the phosphorylation of p38, SAPK/JNK, and Erk1/2 in LNCaP and TRAMP-C2. In vivo, nanaomycin K safely inhibited tumor growth (<i>p</i> = 0.001). In addition, suppression of phospho-Erk1/2 and increased expression of E-cadherin and cleaved-Caspase3 were observed in excised tumors. Nanaomycin K inhibits tumor growth and suppresses migration by inhibiting epithelial-mesenchymal transition in prostate cancer. Its mechanism of action is related to the inhibition of phosphorylation of the MAPK signaling pathway. |
| first_indexed | 2024-03-11T03:52:40Z |
| format | Article |
| id | doaj.art-5d24ea60c60a460f9b2d288aac7ec624 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:52:40Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5d24ea60c60a460f9b2d288aac7ec6242023-11-18T00:47:27ZengMDPI AGCancers2072-66942023-05-011510268410.3390/cancers15102684Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In VivoYuto Hirata0Katsumi Shigemura1Michika Moriwaki2Masato Iwatsuki3Yuki Kan4Tooru Ooya5Koki Maeda6Youngmin Yang7Takuji Nakashima8Hirotaka Matsuo9Jun Nakanishi10Masato Fujisawa11Department of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, JapanDepartment of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, JapanDepartment of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, JapanŌmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo 108-8641, JapanDepartment of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, JapanDepartment of Medical Device Engineering, Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, JapanDepartment of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, JapanDepartment of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, JapanResearch Organization for Nano and Life Innovation, Waseda University, 513 Waseda Tsurumakicho, Shinjuku-Ku, Tokyo 162-0041, JapanResearch Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2 Hachimandai, Tsukuba 305-8043, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, JapanDepartment of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, JapanSince castration-resistant prostate cancer (CRPC) acquires resistance to molecularly targeted drugs, discovering a class of drugs with different mechanisms of action is needed for more efficient treatment. In this study, we investigated the anti-tumor effects of nanaomycin K, derived from “<i>Streptomyces rosa</i> subsp. <i>notoensis</i>” OS-3966. The cell lines used were LNCaP (non-CRPC), PC-3 (CRPC), and TRAMP-C2 (CRPC). Experiments included cell proliferation analysis, wound healing analysis, and Western blotting. In addition, nanaomycin K was administered intratumorally to TRAMP-C2 carcinoma-bearing mice to assess effects on tumor growth. Furthermore, immuno-histochemistry staining was performed on excised tissues. Nanaomycin K suppressed cell proliferation in all cell lines (<i>p</i> < 0.001) and suppressed wound healing in TRAMP-C2 (<i>p</i> = 0.008). Nanaomycin K suppressed or showed a tendency to suppress the expression of N-cadherin, Vimentin, Slug, and Ras in all cell lines, and suppressed the phosphorylation of p38, SAPK/JNK, and Erk1/2 in LNCaP and TRAMP-C2. In vivo, nanaomycin K safely inhibited tumor growth (<i>p</i> = 0.001). In addition, suppression of phospho-Erk1/2 and increased expression of E-cadherin and cleaved-Caspase3 were observed in excised tumors. Nanaomycin K inhibits tumor growth and suppresses migration by inhibiting epithelial-mesenchymal transition in prostate cancer. Its mechanism of action is related to the inhibition of phosphorylation of the MAPK signaling pathway.https://www.mdpi.com/2072-6694/15/10/2684nanaomycin K<i>streptomyces</i>prostate cancercastration-resistant prostate cancertumor growthmigration |
| spellingShingle | Yuto Hirata Katsumi Shigemura Michika Moriwaki Masato Iwatsuki Yuki Kan Tooru Ooya Koki Maeda Youngmin Yang Takuji Nakashima Hirotaka Matsuo Jun Nakanishi Masato Fujisawa Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo Cancers nanaomycin K <i>streptomyces</i> prostate cancer castration-resistant prostate cancer tumor growth migration |
| title | Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo |
| title_full | Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo |
| title_fullStr | Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo |
| title_full_unstemmed | Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo |
| title_short | Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by <i>Streptomyces</i> sp., on Prostate Cancer Cell Lines In Vitro and In Vivo |
| title_sort | growth and migration blocking effect of nanaomycin k a compound produced by i streptomyces i sp on prostate cancer cell lines in vitro and in vivo |
| topic | nanaomycin K <i>streptomyces</i> prostate cancer castration-resistant prostate cancer tumor growth migration |
| url | https://www.mdpi.com/2072-6694/15/10/2684 |
| work_keys_str_mv | AT yutohirata growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT katsumishigemura growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT michikamoriwaki growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT masatoiwatsuki growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT yukikan growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT tooruooya growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT kokimaeda growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT youngminyang growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT takujinakashima growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT hirotakamatsuo growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT junnakanishi growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo AT masatofujisawa growthandmigrationblockingeffectofnanaomycinkacompoundproducedbyistreptomycesisponprostatecancercelllinesinvitroandinvivo |