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KMID : 0613820190290090941
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Journal of Life Science
2019 Volume.29 No. 9 p.941 ~ p.948
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Ziyuglycoside II Attenuates Tumorigenesis in Experimental Colitis-associated Colon Cancer
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Cheon Hye-Jin
Kim Jin-Kyung
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Abstract
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Colorectal cancer is a major health problem in industrialized countries. Ziyuglycoside II (3β-3-α-1- arabinopyranosyloxy-19-hydroxyurs-12-en-28-oicacid), a triterpenoid saponin isolated from the roots of Sanguisorba officinalis L., possesses antioxidant, antiangiogenic, and anticancer properties. However, the therapeutic function of ziyuglycoside II in colitis-associated colorectal carcinogenesis is undefined. In the present study, the effect of ziyuglycoside II on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS) was explored. The AOM model recapitulates many features of human colon cancer, but it lacks an inflammatory component. DSS induces colitis and promotes AOM-induced colon cancer in mice. BALB/c mice were injected with AOM and administered 2% DSS in drinking water. The mice were given ziyuglycoside II (1 or 5 mg/kg) orally three times per week, and colonic tissue was collected at 64 days. Administration of ziyuglycoside II markedly diminished the formation of colonic tumors. Western blot and immunohistological analyses showed that ziyuglycoside II noticeably decreased nuclear factor kappa-B-positive cells and levels of inflammation-related proteins, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6 in colon tissue. It also prompted apoptosis. Ziyuglycoside II treatment augmented cleaved forms of caspase-3, caspase-7, and poly (ADP-ribose) polymerase in colonic tissues. In conclusion, ziyuglycoside II could defend against colitis-associated tumorigenesis in mice by inhibiting inflammation and inducing apoptosis. This shows a promising chemopreventive potential for its use in colitis-associated colon cancer.
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KEYWORD
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Apoptosis, colitis-associated colon cancer, inflammation, NF-κB, ziyuglycoside II
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