Int J Biol Sci 2018; 14(11):1521-1534. doi:10.7150/ijbs.25334
Butein suppresses hepatocellular carcinoma growth via modulating Aurora B kinase activity
1. Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, P.R. China
2. State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan, 410000, P.R. China
3. Department of Infectious Diseases, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, P.R. China
4. Shandong Lvdu Bio-Industry Co., Ltd., Binzhou, Shandong 256600, P.R. China
5. Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
6. Changsha Stomatological Hospital, Changsha, Hunan 410004, P.R. China.
7. School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China
8. Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
9. Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
* These authors contributed equally to this work.
Aurora B is aberrantly expressed in various tumors and shown to be a promising target for cancer therapy. Butein, a chalcone isolated from Rhus cerniciflua, has demonstrated antitumor activities in different cancers. In this study, we aimed to validate whether Aurora B kinase was the direct target of butein to exhibit its potency in hepatocellular carcinoma (HCC). Comparing with the normal cell line and tissue, Aurora B was overexpressed in all tested HCC cells and the majority of tumor tissue. Knocking down of Aurora B with shRNA substantially inhibited HCC cell proliferation, colony formation and delayed tumor growth in nude mice. Except computer docking, a series of kinase assays revealed butein directly interacted with Aurora B and inhibited its kinase activity. Along with the decrease of Aurora B and histone H3 phosphorylation, HCC cells were induced G2/M cell cycle arrest and subjected to cell apoptosis. Butein-mediated antitumor activities were substantially impaired in Aurora B knockdown cells, suggesting Aurora B was an important target of butein in HCC. Oral administration of butein substantially restrained HCC xenograft growth and the expressions of Ki67 and phosphor-histone H3 were significantly decreased in butein-treated tissue. To the best of our knowledge, our studies revealed that Aurora B was the direct target of butein in HCC.
Keywords: Apoptosis, Aurora B, Butein, cell cycle arrest, Hepatocellular carcinoma
Zhou Y, Li M, Yu X, Liu T, Li T, Zhou L, Liu W, Li W, Gao F. Butein suppresses hepatocellular carcinoma growth via modulating Aurora B kinase activity. Int J Biol Sci 2018; 14(11):1521-1534. doi:10.7150/ijbs.25334. Available from http://www.ijbs.com/v14p1521.htm