title: Dehydroandrographolide inhibits oral cancer cell migration and invasion through NF-κB-, AP-1-, and SP-1-modulated matrix metalloproteinase-2 inhibition.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  DA inhibits the invasion of human oral cancer cells and is a potential chemopreventive agent against oral cancer metastasis.
authors.affiliation: 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.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wei-En
authors.initials: WE
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Chien
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lo
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Hsi
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011480:Protease Inhibitors / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D016328:NF-kappa B; D011480:Protease Inhibitors; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D020778:Matrix Metalloproteinase 2; C478098:dehydroandrographolide
keywords: Dehydroandrographolide; Invasion; Matrix metalloproteinase-2; Migration; Oral cancer