Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases.
Licochalcone A, a major phenolic constituent of the licorice species Glycyrrhiza inflata, has been proven to possess various biological benefits including anti-cancer activity. However, the detailed effects and molecular mechanisms of licochalcone A on the invasiveness and metastasis of oral cancer cells have not been fully understood. Thus, SCC-25 oral cancer cells were subjected to a treatment with licochalcone A at indicated concentrations (25, 50, and 100 μg/mL) for 36 h and then analyzed for the effect of licochalcone A on the cell migration and invasion. In vitro assays, including wound healing, cell adhesion, and cell invasion/migration assays, revealed that licochalcone A treatment significantly inhibited the cell migration/invasion capacities of SCC-25 cells. Also, results of zymography and Western blotting showed that activity and protein level of matrix metalloproteinase-2 (MMP-2) was suppressed, but TIMP-2 level was increased, indicating the important role of MMP-2 and TIPM-2 in anti-metastatic regulation of SCC-25 cells. Furthermore, licochalcone A was shown to suppress the nuclear factor-kappa B (NF-κB) signal, as evidenced by the decreased expression of phosphorylated p65 (p-65) protein in licochalcone A-treated SCC-25 cells. Notably, we also found that licochalcone A treatment increased the expression of the epithelial marker E-cadherin and decreased the expression of mesenchymal markers N-cadherin in SCC-25 cells. This is the first report describing the effects and possible mechanisms of licochalcone A on tumor invasion and metastasis of SCC-25 cells. Taken together, our findings support that licochalcone A can be developed to a potent anti-metastatic candidate for oral cancer therapy.
Department of Stomatology, The General Hospital of the Second Artillery Corps of Chinese PLA, Beijing, 100088, People's Republic of China.
Huan
H
Shen
Guang
G
Zeng
Guo
G
Tang
Xingwei
X
Cai
Lixia
L
Bi
Changcheng
C
Huang
Yongjin
Y
Yang
D015820:Cadherins / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D014945:Wound Healing / Q000187:drug effects
D015820:Cadherins; D047188:Chalcones; D016328:NF-kappa B; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; C070840:licochalcone A