title: Terminalia catappa Exerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity.
abstract: High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified that Terminalia catappa leaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1.
authors.affiliation: School of Medicine, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan ; Department of Emergency Medicine, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan ; Department of Emergency Medicine, Chung Shan Medical University Hospital, 110 Chien-Kuo N. Road, Section 1, Taichung 402, Taiwan.
authors.forename: Chao-Bin
authors.initials: CB
authors.lastname: Yeh
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.forename: Pen-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang