Schizandrin의 신혈관형성억제에 의한 항암효과
Antitumor Effect of Schizandrin by Inhibiting Angiogenesis
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초록
Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 μg/ml schizandrin showed a significant inhibition by 73.79 ± 6.43% and 90.46 ± 1.72%, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 μg/head significantly inhibited the tumor-induced angiogenesis by 68.04 ± 32.21% and 103.8 ± 34.99% compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 μg/head schizandrin significantly decreased the metastatic lung tumor by 37.51 ± 8.15% and 75.53 ± 4.38% compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.
Abstract
Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 μg/ml schizandrin showed a significant inhibition by 73.79 ± 6.43% and 90.46 ± 1.72%, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 μg/head significantly inhibited the tumor-induced angiogenesis by 68.04 ± 32.21% and 103.8 ± 34.99% compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 μg/head schizandrin significantly decreased the metastatic lung tumor by 37.51 ± 8.15% and 75.53 ± 4.38% compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.
참고문헌 (24)
- Mina, L. A., "Rethinking the metastatic cascade as a therapeutic target", Nat Rev Clin Oncol, 8(6), pp.325~332 (2011)
- Bailer, J. C., "Cancer undefeated", N Eng J Med, 336, pp.1567~1575 (1997)
- Poprach, A., "Cardiotoxicity of drugs used in oncology", Klin Onkol, 21(5), pp.288~293 (2008)
- Lee, S. J., "1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose blocks endothelial cell growth and tube formation through inhibition of VEGF binding to VEGF receptor", Cancer Lett, 208(1), pp.89~94 (2004)
- Han, K. Y., "Polyphosphate blocks tumour metastasis via anti-angiogenic activity", Biochem J, 406(1), pp.49~55 (2007)
- Folkman, J., "Angiogenic factor", Science, 235, pp.442~447 (1987)
- Folkman, J., "Relation of vascular proliferation to tumor growth", Int Rev Exp Path, 16, pp.207~248 (1976)
- Folkman, J, "Fundamental concepts of the angiogenic process", Curr Mol Med, 3, pp.643~651 (2003)
- Yamakawa, S., "(-)-Epigallocatechin gallate inhibits membrane-type 1 matrix metalloproteinase, MT1-MMP, and tumor angiogenesis", Cancer Lett, 210, pp.47~55 (2004)
- Igura, K., "Resveratrol and quercetin inhibit angiogenesis in vitro", Cancer Lett, 171, pp.11~16 (2001)
- Liu, Z., "Gallic acid is partially responsible for the antiangiogenic activities of Rubus leaf extract", Phytother Res, 20(9), pp.806~813 (2006)
- Min, J. K., "Capsaicin inhibits in vitro and in vivo angiogenesis", Cancer Res, 64, pp.644~651 (2004)
- Yim, S. Y., "Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma", Mol Med Report, 2(5), pp.725~732 (2009)
- Park, J. Y., "The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta", J Ethnopharmacol, 121(1), pp.69~73 (2009)
- Li, X. J., "Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations", Free Radic Biol Med, 9(2), pp.99~104 (1990)
- Kim, S. H., "Structural identification and antioxidant properties of major anthocyanin extracted from Omija(Schizandra chinensis)fruit", J Food Sci, 74(2), pp.C134~C140 (2009)
- Ikeya, Y., "Isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schizandrin", Chem Pharm Bull, 27(6), pp.1383~1394 (1979)
- Oh, S. Y., "Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit of Schisandra chinensis", BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 74(2), pp.285~291, JAPAN SOC BIOSCI BIOTECHN AGROCHEM
- Lu, H., "Anti-oxidant activity of dibenzocyclooctene lignans isolated from Schisandraceae", Planta Med, 58(4), pp.311~313 (1992)
- 유강열, "Schizandrin prevents damage of murine mesangial cells via blocking NADPH oxidase-induced ROS signaling in high glucose", FOOD AND CHEMICAL TOXICOLOGY, 50(3-4), pp.1045~1053 (2012), PERGAMON-ELSEVIER SCIENCE LTD
- Mak, D. H., "Alterations in susceptibility to carbon tetrachloride toxicity and hepatic antioxidant", detoxification system in streptozotocin-induced short-term diabetic rats : effects of insulin and Schisandrin B treatment, 1997, pp.175(1), 225~232
- Gu, B. H., "Eoxyschisandrin inhibits H2O2-induced apoptotic cell death in intestinal epithelial cells through nuclear factor-kappaB", Int J Mol Med, 26(3), pp.401~406 (2010)
- Kronenberg, F., "The future of complementary and alternative medicine for cancer", Cancer Invest, 23, pp.420~426 (2005)
- Dang, C. V., "Oncogenic alteration of metabolism", Trends Biochem Sci, 24, pp.68~72 (1999)
