Antrodia cinnamomea fruiting bodies extract suppresses the invasive potential of human liver cancer cell line PLC/PRF/5 through inhibition of nuclear factor kappaB pathway.
In this study, we first report the anti-invasive effect of ethylacetate extract from Antrodia cinnamomea (EAC) fruiting bodies in the human liver cancer cell line PLC/PRF/5. Treatment with EAC decreased the cancer invasion of PLC/PRF/5 cells in a dose-dependent manner. This effect was strongly associated with a concomitant decrease in either the level or activity of VEGF, MMP-2, MMP-9 and MT1-MMP, and an increase in the expression of TIMP-1 and TIMP-2. EAC inhibited constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity. Furthermore, EAC also inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of MMP-9 and VEGF, and the invasion of cancer cells. EAC also exhibited an inhibitory effect on angiogenesis in a Matrigel Plug Angiogenesis Assay. Further investigation revealed that EAC's inhibition of cancer cell growth and invasion was also evident in a nude mice model. Our results indicate that EAC inhibits the activation of NF-kappaB, and may provide a molecular basis for drug development using EAC as an anti-invasive agent in the prevention and treatment of cancer.
Hsu
Ya-Ling
YL
Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Kuo
Po-Lin
PL
Cho
Chien-Yu
CY
Ni
Wen-Chiu
WC
Tzeng
Tz-Fei
TF
Ng
Lean-Teik
LT
Kuo
Yueh-Hsiung
YH
Lin
Chun-Ching
CC
D000085:Acetates / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020072:Polyporales / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000085:Acetates; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D010936:Plant Extracts; D012997:Solvents; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; C007650:ethyl acetate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14