Anti-Proliferative Activity of Ethanol Extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) Through Cyclin D1 Proteasomal Degradation in Human Colorectal Cancer Cells
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In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor GSK3β but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through GSK3β-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.
Abstract
In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor GSK3β but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through GSK3β-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.
참고문헌 (27)
- Alao, J.P., "The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention", Mol. Cancer, 6, pp.24~ (2007)
- Alt, J. R., "Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation", Genes Dev, 14, pp.3102~3114 (2000)
- Bahnassy, A. A., "Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients", BMC Gastroenterol, 23, pp.22~24 (2004)
- Baker, D. D., "The value of natural products to future pharmaceutical discovery", Nat. Prod. Rep, 24, pp.1225~1244 (2007)
- Casanovas, O., "Osmotic stress regulates the stability of cyclin D1 in a p38SAPK2-dependent manner", J. Biol. Chem, 275, pp.35091~35097 (2000)
- Cragg, G. M., "Natural products in drug discovery and development", J. Nat. Prod, 60, pp.52~60 (1997)
- Diehl, J. A., "Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization", Genes Dev, 12, pp.3499~3511 (1998)
- Eo, H. J., "Silymarin induces cyclin D1 proteasomal degradation via its phosphorylation of threonine-286 in human colorectal cancer cells", Int. Immunopharmacol, 24, pp.1~6 (2015)
- Gillett, C., "Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining", Cancer Res, 54, pp.1812~1817 (1994)
- Holland, T.A., "Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21(WAF1", CIP1) expression and correlates with patient survival, 2001, pp.95, 302~306
- Kato, A., "Chemopreventive effect of resveratrol and apocynin on pancreatic carcinogenesis via modulation of nuclear phosphorylated GSK3beta and ERK1", 2, 2015, pp.6, 42963~42975
- Kim, M.K., "Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1", 2 dependent way in human colorectal cancer cells, 2015, pp.101, 162~168
- Lee, S.H., "Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells", Mol. Carcinogenesis, 47, pp.197~208 (2008)
- Mermelshtein, A., "Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas", Brit. J. Cancer, 93, pp.338~345 (2005)
- Musgrove, E.A., "Cyclin D as a therapeutic target in cancer", Nat. Rev. Cancer, 11, pp.558~572 (2011)
- Okabe, H., "A critical role for FBXW8and MAPK in cyclin D1 degradation and cancer cell proliferation", PloS One, 1, pp.e128~ (2006)
- Park, G.H., "The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1", 2, JNK and GKS3beta-dependent threonine-286 phosphorylation in human colorectal cancer cells, 2016, pp.95, 142~148
- Park, G.H., "Anti-cancer activity of Psoralea fructus through the down regulation of cyclin D1 and CDK4 in human colorectal cancer cells", BMC Complement. Altern. Med, 16, pp.373~ (2016)
- 박광훈, "Anticancer Activity of the Safflower Seeds (Carthamus tinctorius L.) through Inducing Cyclin D1 Proteasomal Degradation in Human Colorectal Cancer Cells", 한국자원식물학회지, 29(3), pp.297~304 (2016), 한국자원식물학회[DOI]
- Russell, A., "Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer", Oncogene, 18, pp.1983~1991 (1999)
- Siegel, R.L., "Colorectal cancer statistics, 2017", CA Cancer J. Clin, 67, pp.177~193 (2017)
- Thoms, H.C., "p38-mediated inactivation of cyclin D1", cyclin-dependent kinase 4 stimulates nucleolar translocation of RelA and apoptosis in colorectal cancer cells, 2007, pp.67, 1660~1669
- Wang, Y., "Parasitic loranthus from Loranthaceae rather than Viscaceae potently inhibits fatty acid synthase and reduces body weight in mice", J. Ethnopharmacol, 118, pp.473~478 (2008)
- Wen, C.C., "Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication", J. Trad. Complement. Med, 1, pp.41~50 (2011)
- Woo, I.S., "Metronomic chemotherapy in metastatic colorectal cancer", Cancer Lett, 400, pp.319~324 (2017)
- Zhang, L., "Immunomodulatory activities of polysaccharides isolated from Taxillus chinensis and Uncaria rhyncophylla", Carbohydr. Polym, 98, pp.1458~1465 (2013)
- Zhang, L., "Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds", J. Agric. Food Chem, 59, pp.12361~12367 (2011)