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Antiproliferative Effect of RST Associated with the Inhibition of Cyclooxygenase-2 Expression and Prostaglandin E2 Release in Human Lung Carcinoma Cells  

Kim, Kang-Tae (Department of Pathology, College of Oriental Medicine, Dongeui University)
Eom, Hyun-Sup (Department of Pathology, College of Oriental Medicine, Dongeui University)
Chi, Gyoo-Yong (Department of Pathology, College of Oriental Medicine, Dongeui University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.21, no.4, 2007 , pp. 907-915 More about this Journal
Abstract
In this study the effect of water extract of Sophora tonkinensis Gapnep (RST) was investigated on the growth of human lung carcinoma A549 cells. Exposure of A549 cells to RST resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay. The antiproliferative effect by RST treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. RST treatment did not induce the cell cycle arrest and the levels of tumor suppressor p53 as well as cyclin-dependent kinase inhibitor p21(WAF1/CIP1). It was found that RST treatment decreased the levels of cyclooxygenase (COX) -2 mRNA and protein expression without significant changes in the expression of COX-1 and inducible nitric oxide synthase (iNOS), which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. RST treatment also slightly inhibited the levels of human telomerase reverse transcriptase (hTERT) mRNA and protein expression, and the activity of telomerase. Taken together, these findings suggested that RST-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the inhibition of COX-2 expression and PGE2 production. These results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of RST.
Keywords
Sophora tonkinensis; COX-2; PGE2; A549 cell;
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1 이현우, 이관호. 폐암의 조기진단. 영남의대학술지 15(2), 1998
2 Xiong, Y., Hannon, G.J., Zhang, H., Casso, D., Kobayashi, R. and Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature, 366: 701-704, 1993   DOI   ScienceOn
3 Vainio, H. Is COX-2 inhibition a panacea for cancer prevention? Int. J. Cancer 94: 613-614, 2001   DOI   ScienceOn
4 Poole, J.C., Andrews, L.G. and Tollefsbol, T.O. Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269: 1-12, 2001   DOI
5 Kyo, S. and Inoue, M. Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy. Oncogene 21: 688-697, 2002   DOI   ScienceOn
6 Cerni, C. Telomeres, telomerase, and myc. An update, Mutat. Res. 462: 31-47, 2000   DOI   ScienceOn
7 Cerni, C. Telomeres, telomerase, and myc. An update, Mutat. Res. 462: 31-47, 2000   DOI   ScienceOn
8 Giercksky, K.E. COX-2 inhibition and prevention of cancer. Best Pract. Res. Clin. Gastroenterol 15: 821-833, 2001   DOI
9 최남경, 윤경은, 허대석, 김윤이, 이승미, 박병주. 한국노인약물역학코호트에서 폐암 발생률, 사망률 및 생존율. 1994-1998. 한국역학회지 24(2), 2002
10 Zeng, Y.X. and El-Deiry, W.S. Regulation of p21WAF1/ CIP1 expression by p53-independent pathways. Oncogene 12: 1557-1564, 1996
11 Dempke, W., Rie, C., Grothey, A. and Schmoll, H.J. Cyclooxygenase-2: a novel target for cancer chemotherapy? J. Cancer Res. Clin. Oncol. 127: 411-417, 2001   DOI   ScienceOn
12 민홍규. Gerbil의 全腦虛血에 대한 廣豆根의 신경손상방어효능 연구. 경희대학교 한의학과 대학원 석사학위논문, 2002
13 배현옥, 임창경, 장선일, 한동민, 안원근, 윤유식, 전병훈, 김원신, 윤용갑. 항 백혈병작용에 관련된 천연물의 자료조사. 동의생리병리학회지 17(3), 2003
14 Tchou, W.W., Rom, W.N. and Tchou-Wong, K.M. Novel form of p21 (WAF1/CIP1/SDI1) protein in phorbol ester-induced G2/M arrest. J. Biol. Chem. 271: 29556-29560, 1996   DOI   ScienceOn
15 김재동, 윤임중. 정상 및 암세포에서 $SiO_2$, Crocidolite, MMF가 Telomerase 활성에 미치는 영향. 한국의 산업의학, 36(3), 1997
16 Thun, M.J., Henley, S.J. and Patrono, C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J. Natl. Cancer Inst. 94: 252-266, 2002   DOI   ScienceOn
17 Yamamoto, Y. and Gaynor, R.B. Therapeutic potential of inhibition of the NF-$\kappa$B pathway in the treatment of inflammation and cancer. J. Clin. Invest., 107: 135-142, 2001   DOI   ScienceOn
18 朴廷顔. 산두근(Sophora subprostrata)의 화학성분 및 항암활성에 대한 연구. 경희대학고 약학과 대학원 석사학위논문, 2002
19 Taylor, W.R. and Stark, G.R. Regulation of the G2/M transition by p53. Oncogene 20: 1803-1815, 2001   DOI   ScienceOn
20 김수만. 산두근이 PC12 세포 및 뇌해마 신경세포의 Glutamate Excitotoxicity에 미치는 영향. 경희대학교 한의학과 대학원 박사학위논문, 2005
21 Narayan, S., Jaiswal, A.S., Multani, A.S. and Pathak, S. DNA damage-induced cell cycle checkpoints involve both p53-dependent and -independent pathways: role of telomere repeat binding factor 2. Br. J. Cancer 85: 898-901, 2001   DOI   ScienceOn
22 강진형. COX 저해제의 항암효과와 암 예방제로서 선택적 COX-2억제제. 암심포지움, 2002(1), 2002
23 지현정. 인체 암 세포주에서 역전사 효소 기능 억제에 의한 Telomerase 활성도와 Telomerase Subunit 발현 변화. 연세대학교 의과학 대학원 석사학위논문, 2001
24 Surh, Y.J., Chun, K.S., Cha, H.H., Han, S.S., Keum, Y.S., Park, K.K. and Lee, S.S. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-$\kappa$B activation. Mutat. Res. pp 480-481, 243-268, 2001
25 김용범. 두경부 편평세포암에서 Human Telomerase Reverse Transcriptase의 발현과 telomerase 활성도와의 상관관계. 경희대학교 의학과 대학원 석사학위논문, 2002
26 Chui, C.H., Lau, F.Y., Tang, J.C., Kan, K.L., Cheng, G.Y., Wong, R.S., Kok, S.H., Lai, P.B., Ho, R., Gambari, R., Chan, A.S. Activities of fresh juice of Scutellaria barbata and warmed water extract of Radix Sophorae Tonkinensis on anti-proliferation and apoptosis of human cancer cell lines. Int J Mol Med, Aug, 16(2):337-341, 2005
27 Park, D.I., Choi, H.Y., Kam, C.W., Park, C., Choi, T.H., Lee, W.H. and Choi, Y.H. Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity. Oncol. Rep. 11: 853-856, 2004
28 이현임. 廣豆根이 白鼠 中大腦動脈 閉鎖에 의한 局所腦虛血損傷에 미치는 保護效果. 경희대학교 동서의학대학원 신경과학 석사학위논문, 2000
29 김선희, 안종석, 김삼용, 유관희, 안병준. TPA로 야기된 HL-60 세포의 기질부착 저해작용을 이용한 Protein Kinase C 저해 생약의 탐색. 대한암학회, 25(1), 1993
30 Vaziri, H., West, M.D., Allsopp, R.C., Davison, T.S., Wu, Y.S., Arrowsmith, C.H., Poirier, G.G. and Benchimol, S. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J. 16: 6018-6033, 1997   DOI   ScienceOn
31 Sawaoka, H., Tsuji, S., Tsujii, M., Gunawan, E.S., Sasaki, Y., Kawano, S. and Hori, M. Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab. Invest. 79: 1469-1477, 1999
32 전국한의과대학 본초학교수(공편). 본초학. 영림사, 1991
33 Li, Y., Jenkins, C.W., Nichols, M.A. and Xiong, Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene 9: 2261-2268, 1994
34 Choi, Y.H., Lee, W.H., Park, K.Y. and Zhang L. p53-independent induction of p21 (WAF1/CIP1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn. J. Cancer Res. 91: 164-173, 2000   DOI
35 Datto, M.B., Yu, Y. and Wang, X.F. Functional analysis of the transforming growth factor $\beta$ responsive elements in the WAF1/Cip1/p21 promoter. J. Biol. Chem. 270: 28623-28628, 1995   DOI
36 Dulic, V., Stein, G.H., Far, D.F. and Reed, S.I. Nuclear accumulation of p21Cip1 at the onset of mitosis: a role at the G2/M-phase transition. Mol. Cell Biol. 18: 546-557, 1998   DOI
37 김명유. 정상인과 백혈병에서 telomerase 활성과 그 subunit인 human telomerase RNA (hTR) 및 human telomerase reverse transcriptase (hTRT) 와 p53 단백발현과의 관계에 대한 연구. 고신대학교 내과학 대학원 박사학위논문, 2001
38 Harper, J.W. Cyclin dependent kinase inhibitors. Cancer Surv. 29: 91-107, 1997
39 Musgrove, E.A., Davison, E.A. and Ormandy, C.J. Role of the CDK Inhibitor p27 (Kip1) in mammary development and carcinogenesis: Insights from knockout mice. J. Mammary Gland Biol. Neoplasia. 9: 55-66, 2004   DOI   ScienceOn