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Growth and Migration Blocking Effect of Nanaomycin K, a Compound Produced by Streptomyces sp., on Prostate Cancer
Yuto Hirata1, Katsumi Shigemura1,2,3,4, Michika Moriwaki1
1Department of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-Ku, Kobe 654-0142, 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.
Insights
Nanaomycin K effectively inhibits prostate cancer growth and migration by targeting the MAPK signaling pathway and epithelial-mesenchymal transition. This natural compound shows promise for treating castration-resistant prostate cancer (CRPC).
Area of Science:
- * Oncology
- * Pharmacology
- * Molecular Biology
Background:
- * Castration-resistant prostate cancer (CRPC) develops resistance to current molecularly targeted drugs, necessitating novel therapeutic agents with distinct mechanisms of action.
- * The need for alternative treatments is driven by the limitations of existing therapies in overcoming drug resistance in advanced prostate cancer.
Purpose of the Study:
- * To investigate the anti-tumor effects and therapeutic potential of nanaomycin K, a compound derived from *Streptomyces rosa* subsp. *notoensis*.
- * To elucidate the mechanism of action of nanaomycin K in prostate cancer, focusing on its impact on cell proliferation, migration, and key signaling pathways.
Main Methods:
- * In vitro studies utilized LNCaP, PC-3, and TRAMP-C2 prostate cancer cell lines to assess nanaomycin K's effects on cell proliferation and wound healing.
- * Western blotting was employed to analyze the expression of epithelial-mesenchymal transition (EMT)-related proteins and MAPK signaling pathway components.
- * In vivo experiments involved intratumoral administration of nanaomycin K in TRAMP-C2 bearing mice, followed by tumor growth assessment and immunohistochemistry analysis of excised tissues.
Main Results:
- * Nanaomycin K significantly suppressed cell proliferation across all tested prostate cancer cell lines (p < 0.001) and inhibited wound healing in TRAMP-C2 cells (p = 0.008).
- * The compound reduced the expression of EMT markers (N-cadherin, Vimentin, Slug) and Ras, and inhibited the phosphorylation of p38, SAPK/JNK, and Erk1/2 in LNCaP and TRAMP-C2 cells.
- * In vivo, nanaomycin K demonstrated a significant inhibition of tumor growth (p = 0.001) with no observed toxicity. Immunohistochemistry revealed suppressed phospho-Erk1/2 and increased E-cadherin and cleaved-Caspase3 in tumors.
Conclusions:
- * Nanaomycin K exhibits potent anti-tumor activity against prostate cancer, including castration-resistant forms, by inhibiting cell proliferation and migration.
- * The mechanism involves the suppression of epithelial-mesenchymal transition (EMT) and the inhibition of MAPK signaling pathway phosphorylation.
- * Nanaomycin K represents a promising therapeutic candidate for prostate cancer, offering a novel mechanism of action against drug-resistant disease.
