Article

Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells

Department of Chinese Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan.
Toxicology Letters (Impact Factor: 3.36). 02/2009; 184(3):204-10. DOI: 10.1016/j.toxlet.2008.11.018
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ABSTRACT Previous studies have revealed that acetaldehyde-induced cell invasion and matrix metalloproteinase-9 (MMP-9) activation and are directly involved in hepatic tumorigenesis and metastasis. Acetaldehyde is an important substance for tumor regression. We designed this study to aid in the development of powerful anti-cancer drugs with specific tumor regression and anti-metastatic potentials. Optimal drugs should possess both specific MMP-9 enzyme and gene transcriptional activities at the molecular level. Hesperidin, a flavonoid present in fruits and vegetables, possess anti-inflammatory and chemopreventive activities. Hesperidin suppressed acetaldehyde-induced cell invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells with acetaldehyde. Hesperidin suppressed acetaldehyde-induced MMP-9 expression through the inhibition of nuclear factor-kappaB (NF-kappaB) and AP-1, and suppressed acetaldehyde-stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory signaling pathways. Hesperidin also inhibited acetaldehyde-induced AP-1 activity by the inhibitory phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling pathways. Results from our study revealed that hesperidin suppressed both acetaldehyde-activated NF-kappaB and activator protein 1 (AP-1) activity by IkappaB, JNK, and p38 signaling pathways. This resulted in the reduction of MMP-9 expression, secretion, and hepatocarcinoma cellular invasion. Our result confirmed the therapeutic potential of hesperidin an anti-metastatic and its involvement in the acetaldehyde-induced cell invasiveness of hepatocellular carcinoma in alcoholic patients.

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Available from: Chia-Chou Yeh, Mar 09, 2015
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    • "In addition, Hsd (50 μM) inhibited acetaldehyde-induced activation of IκB (the principal pathway of NF-κB activation), p38 and JNK (MAP kinase signaling manages the AP-1 activity) phosphorylation, dosedependently . Overall, Hsd was able to suppress MMP-9 transcription, secretion and activity in HepG2 cells, diminishing cellular invasiveness [88]. To have a better perspective of the cellular targets of Hsd/Hst in cancer, the mechanisms discussed in this part including cancer chemoprevention through increasing the antioxidant defense system, inducing apoptosis in cancerous cells, the inhibition of inflammation via decreasing inflammatory cytokines and enzymes, and the inhibition of angiogenesis and metastasis are summarized in Fig. 2. "
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    • "Several studies have reported that hesperidin has anti-inflammatory, antioxidant, anticarcinogenic , and neuroprotective effects (Kara et al., 2014; Yeh et al., 2009). Also, it has a vasoprotective, and cholesterol-lowering properties (Yeh et al., 2009). Hesperidin is a compound with 3 hydroxyl groups that maintain a greater antioxidant potency and ability to activate cellular antioxidant preventing enzymes than other flavanones (Kara et al., 2014). "
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