Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma

• Published in: Scientific reports Vol. 6; no. 1; p. 20253
• Main Authors: Zhu, Yongxia, Ye, Tinghong, Yu, Xi, Lei, Qian, Yang, Fangfang, Xia, Yong, Song, Xuejiao, Liu, Li, Deng, Hongxia, Gao, Tiantao, Peng, Cuiting, Zuo, Weiqiong, Xiong, Ying, Zhang, Lidan, Wang, Ningyu, Zhao, Lifeng, Xie, Yongmei, Yu, Luoting, Wei, Yuquan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.02.2016; Nature Publishing Group
• Subjects: 13/2; 13/31; 13/51; 14/34; 631/67/1059; 631/80/84; 64/60; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Proliferation; Cell Survival - drug effects; Disease Models, Animal; Drug resistance; G2 Phase Cell Cycle Checkpoints - drug effects; Gelatinase B; Humanities and Social Sciences; Humans; Hydroxybenzoates - pharmacology; Matrix metalloproteinase; Melanocytes; Melanoma; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; Melanoma, Experimental; Metalloproteinase; Metastases; Metastasis; Mitochondria - drug effects; Mitochondria - metabolism; multidisciplinary; Neoplasia; Neoplasm Metastasis; Nitrofurans - pharmacology; Science; Side effects; Signal transduction; Src protein; Stat3 protein; Suppressor cells; Transcription; Tumors; Vimentin; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20253

Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo . It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated-Src, phosphorylated-FAK and expression of matrix metalloproteinase (MMP) -2, MMP-9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid-derived suppressor cells (MDSCs). These findings suggested that nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma.