Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity.
We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-α-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-α-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-α significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-α-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-α-induced invasion of LNCaP cells. Compared to untreated controls, TNF-α-stimulated LNCaP cells showed a significant increase in nuclear factor-κB (NF-κB) luciferase activity. However, mangiferin treatment markedly decreased TNF-α-induced NF-κB luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-κB subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-κB-mediated MMP-9 expression.
Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea.
Matharage Gayani
MG
Dilshara
Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea.
Chang-Hee
CH
Kang
Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 47340, Korea.
Yung Hyun
YH
Choi
Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea.
Gi-Young
GY
Kim
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C013592:mangiferin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9