Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood-Cultivated Antrodia cinnamomea, Inhibits Metastasis via Suppression of Integrin-Mediated Adhesion, Migration, and Invasion in Human Hepatoma Cells.
Previous research demonstrated that the ethyl acetate extract from Antrodia cinnamomea suppresses the invasive potential of human breast and hepatoma cells, but the effective compounds are not identified. The main bioactive compounds of A. cinnamomea are ergostane-type triterpenoids, and the content of antcin K is the highest. The objective of this study was to evaluate the antimetastatic activity and mechanisms of antcin K purified from the fruiting body of basswood-cultivated A. cinnamomea on human liver cancer Hep 3B cells. The results showed that adhesion, migration, and invasion of Hep 3B cells were effectively inhibited by antcin K within 24 h of treatment. Antcin K not only reduced the protein expression and activity of MMP-2 and MMP-9 but also down-regulated vimentin and up-regulated E-cadherin in Hep 3B cells. In depth investigation for the molecular mechanism revealed that antcin K could reduce the protein expression of integrin β1, β3, α5, and αv and suppress phosphorylation of FAK, Src, PI3K, AKT, MEK, ERK, and JNK. These results suggested that antcin K was able to inhibit the metastasis of human hepatoma cells through suppression of integrin-mediated adhesion, migration, and invasion. Coupled with these findings, antcin K has a good potential to reduce the risk of liver cancer metastasis.
Ya-Ling
YL
Huang
Yung-Lin
YL
Chu
ΔDepartment of Food Science, Rutgers University, New Brunswick, New Jersey, United States.
Chi-Tang
CT
Ho
§Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Jing-Gung
JG
Chung
Chiao-I
CI
Lai
Yu-Cheng
YC
Su
ΠDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resourceσ, China Medical University, Taichung, Taiwan.
Yueh-Hsiung
YH
Kuo
Lee-Yan
LY
Sheen
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry* / Q000254:growth & development; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002782:Cholestenes / Q000302:isolation & purification / Q000494:pharmacology*; D048690:Fruiting Bodies, Fungal / Q000737:chemistry* / Q000254:growth & development; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D032384:Tilia / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D002782:Cholestenes; D016023:Integrins; C000602429:antcin K
Antrodia cinnamomea; antcin K; epithelial mesenchymal transition (EMT); liver cancer metastasis; matrix metalloproteinases (MMPs)