Nanaomycin K Inhibited Cell Proliferation and Epithelial–Mesenchymal Transition in Renal Cell Carcinoma

Abstract

Nanaomycin K is a natural compound found in the culture broth of “Streptomyces rosa subsp. notoensis” OS-3966. Studies have shown that it inhibits epithelial–mesenchymal transition (EMT), a recognized mechanism of cancer cell migration. Here we investigated the EMT-inhibitory and antitumor effects of nanaomycin K in renal cell carcinoma (RCC). We treated the renal cancer cell line ACHN, Caki-1 and Renca with nanaomycin K and examined its effects on cell proliferation, apoptosis, and expression of EMT and apoptosis markers in vitro and in vivo. Wound healing assays were performed to assess cell migration in vitro, and the mice bearing ACHN tumors were treated intratumorally with nanaomycin K to observe tumor size over time. Nanaomycin K significantly inhibited ACHN, Caki-1 and Renca cell growth and cell migration and significantly induced apoptosis of ACHN in the presence of transforming growth factor (TGF)-β. At the gene level, nanaomycin K increased E-cadherin expression, decreased N-cadherin, Vimentin and Slug expressions, and promoted Caspase-3,8,9 expressions. Intratumor administration of nanaomycin K significantly inhibited tumor growth without apparent adverse events for mice. These results indicate that nanaomycin K inhibit cell growth and EMT in TGF-β-induced advanced RCC, and that nanaomycin K is a potential candidate for the treatment of RCC.