Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by Streptomyces sp., on Prostate Cancer Cell Lines In Vitro and In Vivo

Yuto Hirata; Katsumi Shigemura; Michika Moriwaki; Masato Iwatsuki; Yuki Kan; Tooru Ooya; Koki Maeda; Youngmin Yang; Takuji Nakashima; Hirotaka Matsuo; Jun Nakanishi; Masato Fujisawa

doi:10.3390/cancers15102684

Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by Streptomyces sp., on Prostate Cancer Cell Lines In Vitro and In Vivo

Cancers (Basel). 2023 May 10;15(10):2684. doi: 10.3390/cancers15102684.

Authors

Yuto Hirata¹, Katsumi Shigemura^{1

2

3

4}, Michika Moriwaki¹, Masato Iwatsuki^{5

6}, Yuki Kan¹, Tooru Ooya^{3

4

7}, Koki Maeda², Youngmin Yang², Takuji Nakashima⁸, Hirotaka Matsuo⁹, Jun Nakanishi¹⁰, Masato Fujisawa²

Affiliations

¹ Department of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, Japan.
² Department of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan.
³ Department of Medical Device Engineering, Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan.
⁴ Center for Advanced Medical Engineering Research & Development (CAMED), Kobe University, 1-5-1 Minatojima-minamimachi, Chuoku, Kobe 657-0047, Japan.
⁵ Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo 108-8641, Japan.
⁶ Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo 108-8641, Japan.
⁷ Graduate School of Engineering Kobe University, 1-1 Rokkodai-Cho, Nada-Ku, Kobe 657-8501, Japan.
⁸ Research Organization for Nano and Life Innovation, Waseda University, 513 Waseda Tsurumakicho, Shinjuku-Ku, Tokyo 162-0041, Japan.
⁹ Research Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2 Hachimandai, Tsukuba 305-8043, Japan.
¹⁰ Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan.

Abstract

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 "Streptomyces rosa subsp. notoensis" 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 (p < 0.001) and suppressed wound healing in TRAMP-C2 (p = 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 (p = 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.

Keywords: MAPK signaling pathway; castration-resistant prostate cancer; epithelial mesenchymal transition; migration; nanaomycin K; prostate cancer; streptomyces; tumor growth.

Grants and funding

This research received no external funding.