Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway.
Curcumin, a natural and crystalline compound isolated from the plant Curcuma longa with low toxicity in normal cells, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about antimetastasis effects and mechanism of curcumin in lung cancer. Rac1 is an important small Rho GTPases family protein and has been widely implicated in cytoskeleton rearrangements and cancer cell migration, invasion and metastasis. In this study, we examined the influence of curcumin on in vitro invasiveness of human lung cancer cells and the expressions of Rac1. The results indicate that curcumin at 10 μM slightly reduced the proliferation of 801D lung cancer cells but showed an obvious inhibitory effect on epidermal growth factor or transforming growth factor β1-induced lung cancer cell migration and invasion. Meanwhile, we demonstrated that the suppression of invasiveness correlated with inhibition of Rac1/PAK1 signaling pathways and matrix metalloproteinase (MMP) 2 and 9 protein expression by combining curcumin treatment with the methods of Rac1 gene silence and overexpression in lung cancer cells. Laser confocal microscope also showed that Rac1-regulated actin cytoskeleton rearrangement may be involved in anti-invasion effect of curcumin on lung cancer cell. At last, through xenograft experiments, we confirmed the connection between Rac1 and the growth and metastasis inhibitory effect of curcumin in vivo. In summary, these data demonstrated that low-toxic levels of curcumin could efficiently inhibit migration and invasion of lung cancer cells through inhibition of Rac1/PAK1 signaling pathway and MMP-2 and MMP-9 expression, which provided a novel insight into the molecular mechanism of curcumin against lung cancer.
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China. Electronic address: cqyong117@163.com.
Qing-yong
QY
Chen
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, P.R. China; Department of Pharmacy, The 117th Hospital of PLA, Hangzhou, Zhejiang, 310013, P.R. China.
Ying
Y
Zheng
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
De-min
DM
Jiao
The Second Affiliated Hospital of Shaanxi Chinese Medicine University, Xianyang, Shaanxi, 712000, P.R. China.
Fang-yuan
FY
Chen
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
Hui-zhen
HZ
Hu
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
Yu-quan
YQ
Wu
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
Jia
J
Song
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
Jie
J
Yan
Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China.
Li-jun
LJ
Wu
Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, P.R. China. Electronic address: gy@263.net.
Gui-yuan
GY
Lv
D045744:Cell Line, Tumor; D002465:Cell Movement; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
C107953:RAC1 protein, human; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein; D003474:Curcumin
Actin cytoskeleton; Curcumin; Invasion; MMP-2/9; Migration; Rac1