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.
| Original language | English |
|---|---|
| Article number | 595292 |
| Journal | Evidence-based Complementary and Alternative Medicine |
| Volume | 2012 |
| DOIs | |
| Publication status | Published - 2012 |
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ASJC Scopus subject areas
- Complementary and alternative medicine
Cite this
Terminalia catappa exerts antimetastatic effects on hepatocellular carcinoma through transcriptional inhibition of matrix metalloproteinase-9 by modulating NF-κ B and AP-1 activity. / Yeh, Chao Bin; Hsieh, Ming Ju; Hsieh, Yih Shou; Chien, Ming Hsien; Lin, Pen Yuan; Chiou, Hui Ling; Yang, Shun Fa.
In: Evidence-based Complementary and Alternative Medicine, Vol. 2012, 595292, 2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Terminalia catappa exerts antimetastatic effects on hepatocellular carcinoma through transcriptional inhibition of matrix metalloproteinase-9 by modulating NF-κ B and AP-1 activity
AU - Yeh, Chao Bin
AU - Hsieh, Ming Ju
AU - Hsieh, Yih Shou
AU - Chien, Ming Hsien
AU - Lin, Pen Yuan
AU - Chiou, Hui Ling
AU - Yang, Shun Fa
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870174211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870174211&partnerID=8YFLogxK
U2 - 10.1155/2012/595292
DO - 10.1155/2012/595292
M3 - Article
C2 - 23258989
AN - SCOPUS:84870174211
VL - 2012
JO - Evidence-based Complementary and Alternative Medicine
JF - Evidence-based Complementary and Alternative Medicine
SN - 1741-427X
M1 - 595292
ER -