Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway.
Lung cancer is the leading cause of death among cancers worldwide and non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancer cases. Treatment options for patients with advanced NSCLC have evolved in the last decade with the advent of novel biological agents. Andrographolide, a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to have the potential to be developed as a chemotherapeutic agent. In order to understand the anti-cancer properties of andrographolide, we examined its effect on migration and invasion in human NSCLC A549 cells. The results of wound-healing assay and in vitro transwell assay revealed that andrographolide inhibited dose-dependently the migration and invasion of A549 cells under non-cytotoxic concentrations. Molecular data showed that the effect of andrographolide in A549 cells might be mediated via sustained inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt signal involved in the up-regulation of matrix metalloproteinases (MMPs). Our results showed that andrographolide exerted an inhibitory effect on the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The andrographolide-inhibited MMP-7 expression or activity appeared to occur via activator protein-1 (AP-1) because of its DNA binding activity was suppressed by andrographolide. Additionally, the transfection of Akt over-expression vector (Akt1 cDNA) to A549 cells could result in an increase expression of MMP-7 concomitantly with a marked induction on cell invasion. These findings suggested that the inhibition on MMP-7 expression by andrographolide may be through suppression on PI3K/Akt/AP-1 signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.
Lee
Yi-Chieh
YC
Department of Biological Science and Technology and Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan.
Lin
Hui-Hsuan
HH
Hsu
Chin-Hsun
CH
Wang
Chau-Jong
CJ
Chiang
Tai-An
TA
Chen
Jing-Hsien
JH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt