Shikonin blocks migration and invasion of human breast cancer cells through inhibition of matrix metalloproteinase-9 activation.
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, has been reported to promote tumor cell death. However, there are few reports concerning its effect on metastasis-related cell invasion and migration behavior. In the present study, we investigated the effect of shikonin on human breast cancer invasion and migration. We found that shikonin inhibited phorbol 12-myristate 13-acetate (PMA)-induced cell migration and invasion in MCF-7 breast cancer cells, which was correlated with modulation of matrix metalloproteinase-9 (MMP-9) through suppression of both expression and proteolytic and promoter activity. We also found that shikonin inhibited both MMP-9 expression and promoter activity in MDA-MB‑231 cells with high metastatic potential. These results indicated that shikonin induces the suppression of migration and invasion through modulation of MMP-9 in human breast cancer cells. Therefore, shikonin may be a potential anticancer drug for human breast cancer therapy.
College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Soon Young
SY
Jang
College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Jae Koan
JK
Lee
College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Eun Hyang
EH
Jang
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea.
Seo Young
SY
Jeong
College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Jong-Ho
JH
Kim
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage*; D009285:Naphthoquinones / Q000008:administration & dosage*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives
D061965:Matrix Metalloproteinase Inhibitors; D009285:Naphthoquinones; C016101:shikonin; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate