Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling.
Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time-dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis.
Department of Food Science and Technology, Chung-Ang University , Anseong, 456-756, South Korea.
Cheng
C
Bao
Department of Food Science and Technology, Chung-Ang University , Anseong, 456-756, South Korea.
Min Chae
MC
Kim
Department of Food Science and Technology, Chung-Ang University , Anseong, 456-756, South Korea.
Jing
J
Chen
College of Pharmacy, Dongguk University-Seoul , Goyang, 410-820, South Korea.
Jieun
J
Song
College of Pharmacy, Dongguk University-Seoul , Goyang, 410-820, South Korea.
Hyuk Wan
HW
Ko
Department of Food Science and Technology, Chung-Ang University , Anseong, 456-756, South Korea.
Hong Jin
HJ
Lee
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects
D053823:Hedgehog Proteins; D017879:Isothiocyanates; C473643:sulphoraphene
Hedgehog; breast cancer; invasion; migration; sulforaphene