Downregulation of Cyclin D1 by Sophorae Flos through Proteasomal Degradation in Human Colorectal Cancer Cells
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Although Sophorae Flos (SF) has been reported to exert an anti-cancer activity, molecular targets and mechanisms associated with anti-cancer activity of SF have been unclear. Because cyclin D1 has been regarded as an important regulator in the cell proliferation, we focused cyclin D1 and investigated the effect of SF on the cyclin D1 regulation in light of elucidating the molecular mechanism for SF’s anti-cancer activity. The treatment of SF decreased cellular accumulation of cyclin D1 protein. However, SF did not change the level of cyclin D1 mRNA. Inhibition of proteasomal degradation by MG132 attenuated SF-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with SF. In addition, a point mutation of threonine-286 to alanine attenuated SF-mediated cyclin D1 downregulation. Inhibition of ERK1/2 by a selective inhibitor, PD98059 suppressed cyclin D1 downregulation by SF. From these results, we suggest that SF-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2. SF-induced proteasomal degradation of cyclin D1 might inhibit proliferation in human colorectal cancer cells. The current study provides information on molecular events for an anti-cancer activity of SF
Abstract
Although Sophorae Flos (SF) has been reported to exert an anti-cancer activity, molecular targets and mechanisms associated with anti-cancer activity of SF have been unclear. Because cyclin D1 has been regarded as an important regulator in the cell proliferation, we focused cyclin D1 and investigated the effect of SF on the cyclin D1 regulation in light of elucidating the molecular mechanism for SF’s anti-cancer activity. The treatment of SF decreased cellular accumulation of cyclin D1 protein. However, SF did not change the level of cyclin D1 mRNA. Inhibition of proteasomal degradation by MG132 attenuated SF-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with SF. In addition, a point mutation of threonine-286 to alanine attenuated SF-mediated cyclin D1 downregulation. Inhibition of ERK1/2 by a selective inhibitor, PD98059 suppressed cyclin D1 downregulation by SF. From these results, we suggest that SF-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2. SF-induced proteasomal degradation of cyclin D1 might inhibit proliferation in human colorectal cancer cells. The current study provides information on molecular events for an anti-cancer activity of SF
참고문헌 (23)
- Abe, M, "Analysis of lectin binding properties on human Burkitt’s lymphoma cell lines that show high spontaneous metastasis to distant organs in SCID mice: the binding sites for soybean agglutinin lectin masked by sialylation are closely associated with metastatic lymphoma cells", Pathol. Int, 46, pp.977~983 (1996)
- 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)
- Bahnassy, A.A, "Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients", BMC Gastroenterol, 23, pp.22~24 (2004)
- Barnes, D.M, "Cyclin D1 in breast cancer", Breast Cancer Res. Treat, 52, pp.1~5 (1998)
- Bartkova, J, "Cyclin D1 protein expression and function in human breast cancer", Int. J. Cancer, 57, pp.353~361 (1994)
- Diehl, J.A, "Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization", Genes Dev, 12, pp.3499~3511 (1998)
- Diehl, J.A, "Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway", Genes Dev, 11, pp.957~972 (1997)
- Hall, M, "Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer", Adv. Cancer Res, 68, pp.67~108 (1996)
- Jung, C.H, "Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic rats", Biosci. Biotechnol. Biochem, 70, pp.2556~2559 (2006)
- Kang, S.C, "Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities", Phytother. Res, 20, pp.1017~1019 (2006)
- Kim, B.H, "Anti-inflammatory action of legume isoflavonoid sophoricoside through inhibition on cyclooxygenase-2 activity", Planta Med, 69, pp.474~476 (2003)
- 김병학, "Anti-Inflammatory Mode of Isoflavone Glycoside Sophoricoside by Inhibition of Interleukin-6 and Cyclooxygenase02 in Inflammatory Response", Archives of Pharmacal Research, 26(4), pp.306~311 (2003), 대한약학회
- Kim, J.K, "Nuclear cyclin D1: An oncogenic driver in human cancer", J. Cell. Physiol, 220, pp.292~296 (2009)
- Knudsen, K.E, "Cyclin D1: polymorphism, aberrant splicing and cancer risk", Oncogene, 25, pp.1620~1628 (2006)
- Kwak, Y.T, "IkappaB kinase alpha regulates subcellular distribution and turnover of cyclin D1 by phosphorylation", J. Biol. Chem, 280, pp.33945~33952 (2005)
- Langenfeld, J, "Post-translational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism", Proc. Natl. Acad. Sci. USA, 94, pp.12070~12074 (1997)
- Lee, J.W, "Anti-cancer activity of the flower bud of Sophora japonica L. through upregulating activating transcription factor 3 in human colorectal cancer cells", Korean J. Res. Plants, 28(3), pp.297~304 (2015)
- Lo, Y.H, "Active constituents from Sophora japonica exhibiting cellular tyrosinase inhibition in human epidermal melanocytes", J. Ethnopharmacol, 124, pp.625~629 (2009)
- Okabe, H, "A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation", PloS One, 1, pp.e128~ (2006)
- Shinozaki, H, "Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information", Clin. Cancer Res, 2, pp.1155~1161 (1996)
- Tang, Y.P, "Isolation and identification of antioxidants from Sophora japonica", J. Asian Nat. Prod. Res, 4, pp.123~128 (2002)
- 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
- Vermeulen, K, "The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer", Cell Prolif, 36, pp.131~149 (2003)