alpha-Mangostin, a novel dietary xanthone, suppresses TPA-mediated MMP-2 and MMP-9 expressions through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells.
This study first investigates the anti-metastatic effect of alpha-mangostin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in human breast adenocarcinoma cells, MCF-7. First, the result demonstrated alpha-mangostin could inhibit TPA-induced abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed alpha-mangostin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the downregulation the enzyme activities, protein, and messenger RNA levels of MMP-2 and MMP-9 induced by TPA. Next, alpha-mangostin also strongly inhibited TPA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by alpha-mangostin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could inhibit TPA-induced MMP-2 and MMP-9 expressions along with an inhibition on cell invasion and migration. Presented data reveal that alpha-mangostin is a novel, effective, antimetastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.
Lee
Yuan-Bing
YB
Dept. of Gynecology, Yongkang Veterans Hospital, Tainan, Taiwan.
Ko
Kung-Chung
KC
Shi
Ming-Der
MD
Liao
Yi-Chen
YC
Chiang
Tai-An
TA
Wu
Pei-Fen
PF
Shih
You-Xin
YX
Shih
Yuan-Wei
YW
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
D002273:Carcinogens; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D044004:Xanthones; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate; C021053:mangostin