Title: Sulforaphane suppresses oral cancer cell migration by regulating cathepsin S expression
Abstract: // Chang-Tai Chen 1, 2, * , Ming-Ju Hsieh 3, 4, 5, * , Yi-Hsien Hsieh 6 , Min-Chieh Hsin 3 , Yi-Ting Chuang 3 , Shun-Fa Yang 3, 7 , Jia-Sin Yang 3, 7 and Chiao-Wen Lin 1, 2, 8 1 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 2 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 3 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 4 Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan 5 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan 6 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan 7 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 8 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Chiao-Wen Lin, email: [email protected] Jia-Sin Yang, email: [email protected] Keywords: sulforaphane; cathepsin S; LC3; oral cancer; migration Received: November 09, 2017 Accepted: February 28, 2018 Published: April 03, 2018 ABSTRACT Sulforaphane has been demonstrated to exert numerous biological effects, such as neuroprotective, anti-inflammatory, and anticancer effects. However, the detailed effects of sulforaphane on human oral cancer cell migration and the underlying mechanisms remain unclear. In this study, we observed that sulforaphane attenuated SCC-9 and SCC-14 cell motility and invasiveness by reducing cathepsin S expression. Moreover, sulforaphane increased microtubule-associated protein 1 light chain 3 (LC3) conversion, and the knockdown of LC3 by siRNA increased cell migration ability. Regarding the mechanism, sulforaphane inhibited the cell motility of oral cancer cells through the extracellular signal-regulated kinase (ERK) pathway, which in turn reversed cell motility. In conclusion, sulforaphane suppress cathepsin S expression by inducing autophage through ERK signaling pathway. Thus, cathepsin S and LC3 may be new targets for oral cancer treatment.