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http://dx.doi.org/10.6114/jkood.2019.32.4.001

Anticancer and Signaling Mechanisms of Biologically Active Substances from Orostachys japonicus through Arrest of Cell cycle in Human Melanoma Cells  

Ryu, Deok-Hyun (Dept. of Oriental Medical Ophthalmology & Otolaryngology & Dermatology, College of Oriental Medicine, Daejeon University)
Ryu, Deok-Seon (Dept. of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University)
Publication Information
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology / v.32, no.4, 2019 , pp. 1-12 More about this Journal
Abstract
Objectives : The purpose of this study was to identify the anticancer effect of biological substances of ethylacetate(EtOAc) fraction from Orostachys japonicus(OJEF), their effect on human melanoma A375 cells and the related molecular mechanisms. Methods : The MTS assay was used to confirm the inhibition of cancer cell proliferation in A375 cells. And the $MUSE^{TM}$ analyzer was used to determine the ability of OJEF to induce cell cycle arrest. Western blotting was used to determine the changes in protein expression in A375 cells after treatment with OJEF. Results : OJEF showed cytotoxicity to A375 cells. And cell cycle arrest occurred in G1 phase and G2/M phase owing to inhibition of CDK1, cyclin B1, CDK4, and cyclin D, which are related to cell cycle regulation and cell division control. Conclusion : OJEF is effective in regulating cell cycle of human melanoma cells and thus can be a good theraputic agent to treat patients with melanoma.
Keywords
Melanoma; Orostachys Japonicus; Anticancer; Cell Cycle Arrest;
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1 Yamamoto T, Senba K. Illustration map of cell signaling. (SG Oh and ES Oh trasslation). Seoul:World science. 2006.
2 Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular Targets of Resveratrol: Anti-carcinogenic Mechanisms. Arch Biochem Biophys. 2009;486(2):95-102.   DOI
3 Ryu DS, Kim SH, Kwon JH, et al. Orostachys japonicus induces apoptosis and cell cycle arrest through the mitochondria-dependent apoptotic pathway in AGS human gastric cancer cells. Int J Oncol. 2014;45(1):459-69.   DOI
4 Sekulic A, Haluska P Jr, Miller AJ, Lamo JGD, Ejadi S, Pulido JS, et al. Malignant melanoma in the 21st century: the emerging molecular landscape. Mayo Clinic Proc. 2008;83(7):825-46.   DOI
5 Rigel DS, Carucci JA. Malignant melanoma: prevention, early detection, and treatment in the 21st century. CA Cancer J Clin. 2000;50(4):215-36.   DOI
6 Jo CS and Jo JG. A Literature Review about Orostachys japonicus. J Korean Med Daejeon Univ. 1993;2(2):83-98.
7 Jeong JH, Ryu DS, Suk DH, Lee DS. Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells. BMB REP. 2011;44(6):399-404.   DOI
8 Je Ma C, Jung WJ, Lee KY, Kim YC, Sung SH. Calpain inhibitory flavonoids isolated from Orostacys japonicus. J Enzyme Inhib Medic Chem. 2009;24(3):676-9.   DOI
9 Ryu DS, Lee HS, Lee GS, Lee DS. Effects of the Ethylacetate Extract of Orostachys japonicus on Induction of Apoptosis through the p53-Mediated signaling Pathway in Human Gastric Cancer Cells. Biol Pharm Bull. 2012;35(5):660-5.   DOI
10 Yoon SY, Lee SY, Kim KBWR, Song EJ, Kim SJ, Lee SJ, et al. Antimicrobial activity of the solvent extract from different parts of Orostachys japonicus. J Korean Soc Food Sci Nutr. 2009;38(1):14-8.   DOI
11 Lee SJ, Zhang GF, Sung NJ. Hypolipidemic and hypoglycemic effects of Orostachys japonicus A. Berger extracts in streptozotocin-induced diabetic rats. Nutr Res Pract. 2011;5(4):301-7.   DOI
12 Lee GS, Lee HS, Kim SH, Suk DH, Ryu DS, Lee DS. Anti-cancer activity of the ethylacetate fraction from Orostachys japonicus for modulation of the signaling pathway in HepG2 human hepatoma cells. Food Sci Biotechnol. 2014;23(1):269-75.   DOI
13 Park HJ, Lim SC, Lee MS, Young HS. Triterpene and Steroids from Orostachys japonicus. Kor J Pharmacog. 1994;25(1):20-3.
14 Ryu DS, Baek GO, Kim EY, Kim KH, Lee DS. Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells. BMB REP. 2010;43(11):750-5.   DOI
15 Kim CM, Shin MG, Lee GS, et al. Dictionary of Chinese herbs(7). Seoul:Jungdam. 1998:4042-4.
16 Lee WS, Yun JW, Nagappan A, Jung JH, Yi SM, Kim DH, et al. Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells. Asian Pac J Cancer Prev. 2015;16(2):465-9.   DOI
17 Kim JS, Yoon SH, Ryu BH, Ryu KW. Anti-cancer Effects of Orostachyos Herba on some Kinds of Cancer Cells. Korean J Intern Med. 2005;26(2):333-40.
18 Kim KS, Yea SC, Yoo BC, Cho CK, Lee YW, Yoo HS. Altered Protein Expression in Ovarian and Cervical Cancer Cells by the Treatment of Extracts from Euonymus alatus Sieb, Oldenlandia diffusa(Wild.) Roxburgh, and Orostachys japonicus A. Berger. Korean J Intern Med. 2011;32(1):33-42.
19 Kim JY, Jung EJ, Won YS, Lee JH, Shin DY, Seo KI. Cultivated Orostachys japonicus Induces Apoptosis in Human Colon Cancer Cells. Korean J Food Sci Technol. 2012;44(3):317-23.   DOI
20 Won YS, Lee JH, Kown SJ, Ahn DU, Shin DY, Seo KI. Anticancer Effects of Cultivated Orostachys japonicus on Human Prostate Cancer Cells. Korean J Food Sci Nutr. 2014;43(1):67-73.   DOI
21 Yun KS, Kim YC, Lee JH, Woo HJ. Effect of Orostachys japonicus A. Berger on Apoptosis in K562 Cell Lines. Korean J Intern Med. 2006;27(1):166-77.
22 Oh HS and Kim JH. Effects of Partial Cervus elaphus Linne' Extract on Antitumoral Immune Response in Melanoma-induced Mice. J Korean Oriental Med. 2000;14(1):39-77.
23 Elledge SJ, Harper JW. Cdk inhibitors: on the threshold of checkpoints and development. Curr Opin Cell Biol. 1994;6(6):847-52.   DOI
24 Elwood JM. Melanoma and sun exposure. Semin Oncol. 1996;23(6):650-66.
25 Garbe C, Eigentler TK. Diagnosis and treatment of cutaneous melanoma: state of the art 2006. Melanoma Res. 2007;17(2):117-27.   DOI
26 Pines J. Protein kinases and cell cycle control. Semin Cell Biol. 1994;5(6):399-408.   DOI
27 Ko HS, Kang KW, Kim JH. Anticancer Effects of Gleditsin in Human Mammary Cancer Cells. Yeungnam Univ J Med. 2007;24(2):580-90.
28 Blagosklonny MV, Pardee AB. The Restriction Point of the Cell Cycle. Cell cycle. 2002;1(2):102-9.   DOI
29 Stark GR, Taylor WR. Analyzing the G2/M Checkpoint. Meth Mol Biol. 2004;280(1):51-82.
30 Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131-49.   DOI
31 Cho HK, Yu SJ, Roh JY, Hwang WI, Sohn HJ. Molecular Mechanism of the Antiproliferative Effect by Ginseng Panaxynol on a Human Malignant Melanoma Cell Line, SK-MEL-1. J Ginseng Res. 1999;23(3):190-7.
32 Kwon JH, Lee DS, Jung EC, Kim HM, Kim SB, Ryu DS. Anti-cancer activity of the ethylacetate fraction from Orostachys japonicus in A549 human lung cancer cells by induction of apoptosis and cell cycle arrest. Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology. 2017;7(1):395-405.
33 Lee BM, Shim JS, Kim TS Han DG. Clinical Consideration of 137 Cases of Basal Cell Carcinoma in Face. Arch Craniofac Surg. 2013;14(2):107-10.   DOI
34 Hussein MR, Haemel AK, Wood GS. Apoptosis and melanoma: molecular mechanisms. J Pathol. 2003;199(3):275-88.   DOI
35 Helmbach H, Rossmann E, Kern MA, Schadendorf D. Drug-resistance in human melanoma. Int J Cancer. 2001;93(5):617-22.   DOI
36 Kang YJ, Jung HJ, Yim KI, Lee KY, Lee YS, Kang SJ, et al. Alternation of Apoptosis- Related Proteins(Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesion. Korean J Pathol. 2011;45(3):247-53.   DOI