Emodin, aloe-emodin and rhein inhibit migration and invasion in human tongue cancer SCC-4 cells through the inhibition of gene expression of matrix metalloproteinase-9.
Emodin, aloe-emodin and rhein are major compounds in rhubarb (Rheum palmatum L.), used in Chinese herbal medicine, and found to have antitumor properties including cell cycle arrest and apoptosis in many human cancer cells. Our previous studies also showed that emodin, aloe-emodin and rhein induced apoptosis in human tongue cancer SCC-4 cells. However, the detail regarding emodin, aloe-emodin and rhein affecting migration and invasion in SCC-4 cells are not clear. In the present study, we investigated whether or not emodin, aloe-emodin and rhein inhibited migration and invasion of SCC-4 cells. Herein, we demonstrate that emodin, aloe-emodin and rhein inhibit the protein levels and activities of matrix metalloproteinase-2 (MMP-2) but did not affect gene expression of MMP-2, however, they inhibited the gene expression of MMP-9 and all also inhibited the migration and invasion of human tongue cancer SCC-4 cells. MMP-9 (gelatinase-B) plays an important role and is the most associated with tumor migration, invasion and metastasis in various human cancers. Results from zymography and Western blotting showed that emodin, aloe-emodin and rhein treatment decrease the levels of MMP-2, urokinase plasminogen activator (u-PA) in a concentration-dependent manner. The order of inhibition of associated protein levels and gene expression of migration and invasion in SCC-4 cells are emodin >aloe-emodin >rhein. Our results provide new insight into the mechanisms by which emodin, aloe-emodin and rhein inhibit tongue cancers. In conclusion, these findings suggest that molecular targeting of MMP-9 mRNA expression by emodin, aloe-emodin and rhein might be a useful strategy for chemo-prevention and/or chemo-therapeutics of tongue cancers.
Chen
Ya-Yin
YY
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
Chiang
Su-Yin
SY
Lin
Jaung-Geng
JG
Ma
Yi-Shih
YS
Liao
Ching-Lung
CL
Weng
Shu-Wen
SW
Lai
Tung-Yuan
TY
Chung
Jing-Gung
JG
D000504:Aloe / Q000737:chemistry*; D000880:Anthraquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D000880:Anthraquinones; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004642:Emodin; C020491:rhein