Sulforaphane inhibits TGF-β-induced epithelial-mesenchymal transition of hepatocellular carcinoma cells via the reactive oxygen species-dependent pathway

• Published in: Oncology reports Vol. 35; no. 5; pp. 2977 - 2983
• Main Authors: WU, JINSHENG, HAN, JINGLI, HOU, BENXIN, DENG, CHENGWEI, WU, HUANLIANG, SHEN, LIANGFANG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.05.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Bladder cancer; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell growth; Cell Movement; Cell Shape - drug effects; Colorectal cancer; Development and progression; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Female; G1 Phase Cell Cycle Checkpoints; Gene expression; Genetic aspects; Growth models; Health aspects; Hep G2 Cells; hepatocellular carcinoma; Hepatoma; Humans; Inhibitory Concentration 50; Isothiocyanates - pharmacology; Leukemia; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Medical prognosis; Metastasis; Mice, Inbred BALB C; Mice, Nude; Microscopy; Morphology; Neoplasm Invasiveness; Properties; reactive oxygen species; Reactive Oxygen Species - metabolism; Studies; sulforaphane; Thiocyanates; Thyroid cancer; Transforming Growth Factor beta - physiology; Transforming growth factors; Xenograft Model Antitumor Assays; United States > US; China
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2016.4638

Sulforaphane is recognized as a safe antitumor agent derived from various cruciferous vegetables, including broccoli. It has been demonstrated that sulforaphase is a potent antitumor agent in diverse cancers. However, its effect on hepatocellular carcinoma remains largely unknown. Here, we show that sulforaphane inhibits TGF-β-induced epithelial-mesenchymal transition of hepatocellular carcinoma cell via the reactive oxygen species-dependent pathway. We found sulforaphane inhibited hepatocellular carcinoma cell proliferation in a dose- and time-dependent manner. Sulforaphane induced G0/G1 phase cell cycle arrest and promoted cell apoptosis. A set of experiments showed that sulforaphase inhibited hepatocellular carcinoma cell migration and invasion, inhibited the formation of fibroblast like mesenchymal cells and the expression of Vimentin, but increased the expression of E-cadherin, suggesting sulforaphane suppresses epithelial-mesenchymal transition (EMT) process. Cotreatment with N-acetyl-L-cysteine inhibited sulforaphane-inhibited invasion and upregulation of E-cadherin and almost completely abolished the sulforaphane-induced expression of Vimentin. The effect of sulforaphane on the growth of hepatocellular carcinoma cells was confirmed by a xenograft tumor growth model. All our finding indicated that sulforaphane is a promising and safe strategy for treating hepatocellular carcinoma.