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

• Published in: Cancers 2023-05, Vol.15 (10)
• Main Authors: Hirata, Yuto, Shigemura, Katsumi, Moriwaki, Michika, Iwatsuki, Masato, Kan, Yuki, Ooya, Tooru, Maeda, Koki, Yang, Youngmin, Nakashima, Takuji, Matsuo, Hirotaka, Nakanishi, Jun, Fujisawa, Masato
• Format: Article
• Language: English
• Subjects: Analysis; Cancer; Care and treatment; Growth; Prostate cancer; Stem cells
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15102684

Recent molecularly targeted drugs used to treat castration-resistant prostate cancer (CRPC) soon lose effectiveness as CRPC develops resistance to these therapeutics. New molecularly targeted drugs for effective treatment of CRPC are needed. In this study, we investigated the anticancer activity of nanaomycin K, a novel compound extracted from Streptomyces sp., in CRPC and non-CRPC cell lines. Nanaomycin K significantly inhibited the growth of CRPC and non-CRPC cells by inducing apoptosis through the Caspase-3 pathway. Nanaomycin K also significantly inhibited migration of CRPC, decreasing its invasive potential. The inhibition of migration by nanaomycin K was shown to be mediated by inhibition of Ras, Slug, and MAPK phosphorylation. In vivo, nanaomycin K also significantly and safely inhibited the growth of tumors derived from CRPC. Nanaomycin K's anti-tumor effects on CRPC are achieved in part by inhibiting growth and migration. 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.