Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2.
The antimetastatic properties of soybean saponin were investigated by evaluating matrix metalloproteinase (MMP-2 and MMP-9) production in HT-1080 cells. The mRNA expression levels of MMP-2 and MMP-9 were determined by RT-PCR analysis. The levels of secreted MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were determined by gelatin zymography and/or ELISA. The invasion of a Matrigel-coated membrane by human fibrosarcoma HT-1080 and HT-29 colon cancer cells was quantitatively assessed by counting the migrated cells. The treatment of HT-1080 cells with soybean saponin inhibited the mRNA expression of and reduced the amounts of secreted MMP-2 and MMP-9, whereas it increased the amount of secreted TIMP-2 dose-dependently. Soybean saponin significantly inhibited the invasion of HT-1080 cells through a Matrigel-coated membrane. The antimetastatic properties by soybean saponin were further confirmed by in vivo mice experiment via the tail vein injection of CT-26 colon cancer cells after feeding the mice the dietary soybean saponin. The incidence of metastatic tumor colonization of lungs of mice moderately decreased 2 weeks after the tail vein injection of CT-26 cells. Our current data support the notion that soybean saponin inhibits tumor cell metastasis by suppressing MMP-2 and MMP-9 productions, and stimulating TIMP-2 secretion, thereby suggesting that soybean saponin has a chemopreventive property against cancer metastasis.
Kang
Ji-Hye
JH
Department of Food Science and Nutrition, University of Ulsan, Mugeo-dong, Nam-ku, Ulsan 680-749, Republic of Korea.
Han
In-Hee
IH
Sung
Mi-Kyung
MK
Yoo
Hoon
H
Kim
Young-Gyun
YG
Kim
Jeong-Sang
JS
Kawada
Teruo
T
Yu
Rina
R
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D012503:Saponins / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D012503:Saponins; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9