Ajugalide-B (ATMA) is an anoikis-inducing agent from Ajuga taiwanensis with antiproliferative activity against tumor cells in vitro.
Ajuga taiwanensis is widely used for the treatment of hepatitis and hepatoma in Taiwanese folk medicine. However, its bioactive components and mechanism of action are unclear. Herein, ajugalide-B (ATMA), a neoclerodane diterpenoid isolated from Ajuga taiwanensis, is reported to exhibit high anti-proliferative activity against tumor cell lines from various tissues. These results demonstrate that ATMA disrupts the focal adhesion complex by decreasing phosphorylation of paxillin and focal adhesion kinase (FAK). As a result, anoikis, a specific type of apoptosis caused by detachment of cells, is triggered by activation of caspase-8 in A549 cells. Furthermore, ATMA also blocks anchorage-independent growth and cell migration and, therefore, ATMA may serve as a lead compound for the developing of anti-cancer therapeuties with anoikis-inducing properties.
Division of Herbal Medicine and Natural Product, National Research Institute of Chinese Medicine, Taipei 112, Taiwan, Republic of China.
Chun-Tang
CT
Chiou
Yao-Haur
YH
Kuo
Yu-Yi
YY
Chan
Shin-Hun
SH
Juang
Hsiu-Hui
HH
Chan
Tian-Shung
TS
Wu
D031328:Ajuga / Q000737:chemistry*; D023102:Anoikis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans
D000970:Antineoplastic Agents; D004224:Diterpenes; D045785:Diterpenes, Clerodane; C576146:ajugalide-B; C468586:neoclerodane; D051416:Focal Adhesion Protein-Tyrosine Kinases