Ming-Ju Hsieh1, Jui-Chieh Chen2, Wei-En Yang3, Su-Yu Chien4, Mu-Kuan Chen5, Yu-Sheng Lo6, Yi-Ting Hsi6, Yi-Ching Chuang6, Chia-Chieh Lin6, Shun-Fa Yang7. 1. Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan. 2. Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan. 3. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. 4. Department of Pharmacy, Changhua Christian Hospital, Changhua 500, Taiwan; College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan; Center for General Education, Mingdao University, Changhua 52345, Taiwan. 5. Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan. 6. Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan. 7. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: ysf@csmu.edu.tw.
Abstract
BACKGROUND AND PURPOSE: Oral cancer is a type of head and neck cancer that is characterized by cancerous tissue growth in the oral cavity. Andrographolide and dehydroandrographolide (DA) are the two principal components of Andrographis paniculata (Burm.f.) Nees and are the main contributors to its therapeutic properties. However, the pharmacological activities of DA remain unclear. EXPERIMENTAL APPROACH: In this study, we used wound closure assay and Boyden chamber assay to determine the effects of DA on oral cancer cell migration and invasion. KEY RESULTS: DA treatment significantly inhibited the migration and invasion abilities of SCC9 cells in vitro. Gelatin zymography and Western blotting results revealed that DA inhibited MMP-2 activity and reduced its protein levels. DA inhibited the phosphorylation of ERK1/2, p38, and JNK 1/2 in SCC9 cells. According to the mRNA levels detected using real-time PCR, DA inhibited MMP-2 expression in SCC9 cells. This inhibitory effect was associated with the upregulation of the TIMP-2 and downregulation of NF-κB, AP-1, and SP-1 expression. In addition, DA suppressed carcinoma-associated epithelial-mesenchymal transition in SCC9 cells. Finally, DA administration effectively suppressed MMP-2 expression and tumor metastases in the oral carcinoma xenograft mouse model in vivo. CONCLUSIONS & IMPLICATIONS: DA inhibits the invasion of human oral cancer cells and is a potential chemopreventive agent against oral cancer metastasis.
BACKGROUND AND PURPOSE:Oral cancer is a type of head and neck cancer that is characterized by cancerous tissue growth in the oral cavity. Andrographolide and dehydroandrographolide (DA) are the two principal components of Andrographis paniculata (Burm.f.) Nees and are the main contributors to its therapeutic properties. However, the pharmacological activities of DA remain unclear. EXPERIMENTAL APPROACH: In this study, we used wound closure assay and Boyden chamber assay to determine the effects of DA on oral cancer cell migration and invasion. KEY RESULTS:DA treatment significantly inhibited the migration and invasion abilities of SCC9 cells in vitro. Gelatin zymography and Western blotting results revealed that DA inhibited MMP-2 activity and reduced its protein levels. DA inhibited the phosphorylation of ERK1/2, p38, and JNK 1/2 in SCC9 cells. According to the mRNA levels detected using real-time PCR, DA inhibited MMP-2 expression in SCC9 cells. This inhibitory effect was associated with the upregulation of the TIMP-2 and downregulation of NF-κB, AP-1, and SP-1 expression. In addition, DA suppressed carcinoma-associated epithelial-mesenchymal transition in SCC9 cells. Finally, DA administration effectively suppressed MMP-2 expression and tumor metastases in the oral carcinoma xenograft mouse model in vivo. CONCLUSIONS & IMPLICATIONS: DA inhibits the invasion of humanoral cancer cells and is a potential chemopreventive agent against oral cancer metastasis.
Authors: Jun Zhang; Ke Pu; Suyang Bai; Yukui Peng; Fan Li; Rui Ji; Qinghong Guo; Weiming Sun; Yuping Wang Journal: J Int Med Res Date: 2020-06 Impact factor: 1.671