본문 바로가기
KERD
논문KCI 등재

側柏葉이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향

Effects of Thujae Orientalis Folium (TOF) on Gene Expression of Human melanoma cells (SK-MEL-2)

0

조회

0

다운로드

1

인용

0

참고문헌

키워드

주제분류한의학

초록

Objecitve : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2,was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5,PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

Abstract

Objecitve : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2,was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5,PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

참고문헌 (55)

  1. 이미우, "한국인에서의 악성 흑색종에 대한 임상 및 병리 조직학적 연구 - 대한피부과학회 피부병리연구분과위원회 공동연구-", 대한피부과학회지, 41(1), pp.43~47 (2003), 대한피부과학회
  2. 申佶求, "申氏本草學", pp.117~176 (1998), 壽文社
  3. 全國韓醫科大學本草學敎授共, "本草學", pp.395~495 (1991), 永林社
  4. 吳儀洛, "本草從新", pp.107~108 (1982), 杏林書院
  5. 辛民敎, "鄕藥集成方", pp.1039~ (1989), 永林社
  6. 楊東喜, "本草備要解釋", pp.309~310 (1991), 一中社
  7. 汪認庵, "本草易讀", pp.284~285 (1987), 人民衛生出版社
  8. 임종임, "측백엽 추출물의 항산화 효과", 서울大學校藥學論文集, 26, pp.7~14 (2001)
  9. 이수형, "측백엽 메탄올 추출물이 멜라닌 형성에 미치는 영향" (2004), 원광대 대학원
  10. 탁민진, "측백엽 추출물의 발모효과에 관한 실험적 연구" (2006), 우석대 대학원
  11. 천현자, "Quercetin의 Melan-a 멜라닌세포의 멜라닌합성에 미치는 영향", 생약학회지, 33(3), pp.245~251 (2002), 한국생약학회
  12. 송화영, "백자인과 측백엽의 성분인 myricetin이 멜라닌 생성에 미치는 영향" (2004), 원광대대학원
  13. Roslev P, "Application of a Tetrazolium Salt with a Water-Soluble Formazan as an Indicator of Viability in Respiring Bacteria", Appl Environ Microbiol, 59(9), pp.2891~2896 (1993)
  14. Florell SR, "Preservation of RNA for functional genomic studies: a multidisciplinary tumor bank protocol", Mod Pathol, 14(2), pp.116~128 (2001)
  15. Weis S, "Quality control for microarray analysis of human brain samples: The impact of postmortem factors, RNA characteristics, and histopathology", J Neurosci Methods, 165(2), pp.198~209 (2007)
  16. Zahurak M, "Pre-processing Agilent microarray data", BMC Bioinformatics, 8, pp.142~ (2007)
  17. Pavlicek A, "Free-Tree--freeware program for construction of phylogenetic trees on the basis of distance data and bootstrap", jackknife analysis of the tree robustness. Application in the RAPD analysis of genus Frenkelia, 1999, pp.45(3), 97~99
  18. Balch CM, "Cutaneous Melanoma : Clinical management and treatment result world-wide", pp.13~506 (1985), JB Lippincott
  19. 이동훈, "최근 12년간 악성 흑색종의 임상 및 병리조직학적 연구", 대한피부과학회지, 40(8), pp.914~923 (2002), 대한피부과학회
  20. Jang KA, "악성 흑색종의 임상 및 병리조직학적 고찰", Korean J Dermatol, 38, pp.1435~1443 (2000)
  21. Won YH, "Clinical and histopathologic study of malignant melanoma (1980-1990.4)", Korean J Dermatol, 29, pp.193~202 (1991)
  22. Cho KH, "Clinical and histopathologic study of acral melanoma", 27, pp.388~394 (1989)
  23. Gillies Gg, "Incidence. Incidence of nonmelanocytic skin cancer treated in Australia", Br Med J, 296, pp.13~ (1998)
  24. Magnus K, "The nordic profile of skin cancer incidence. A comparative epidemiological study of the three main types of skin cancer", Int J Cancer, 47, pp.12~19 (1991)
  25. 문구, "암 동서의 결합치료", pp.93~97 (1999), 신이출판사
  26. 한진근, "楡白皮 추출물이 인간의 피부 세포 재생 및 악성 흑색종 세포에 미치는 영향", 한방안이비인후피부과학회지, 20(3), pp.81~97 (2007), 대한한방안이비인후피부과학회
  27. 박용호, "DNA chip을 이용한 조각자 추출물의 인간유래 악성 종양에 미치는 영향", 한방안이비인후피부과학회지, 21(1), pp.55~69 (2008), 대한한방안이비인후피부과학회
  28. 김대수, "忍冬藤이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향", 한방안이비인후피부과학회지, 22(1), pp.11~32 (2009), 대한한방안이비인후피부과학회
  29. 박대중, "三白草 에탄올추출물의 항산화능 및 피부 미백작용 연구", 대한본초학회지, 23(2), pp.193~202 (2008), 대한본초학회
  30. Kimizuka F, "DNA chip technologies and their applications: towards functional genomics", Tanpakushitsu Kakusan Koso, 13, pp.2004~2011 (1998)
  31. Sokol DL, "Real time detection of DNA.RNA hybridization in living cells", Proc Natl Acad Sci USA, 95(20), pp.11538~11543 (1998)
  32. Schroeder A, "The RIN: an RNA integrity number for assigning integrity values to RNA measurements", BMC Mol Biol, 7, pp.3~ (2006)
  33. Dunham I, "The DNA sequence of human chromosome 22", Nature, 402(6761), pp.489~495 (1999)
  34. Shu, H B, "Casper is a FADD- and caspase-related inducer of apoptosis", Immunity (UNITED STATES), 6(6), pp.751~763 (1997)
  35. Micheau, Olivier, "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes", Cell, 114(2), pp.181~190 (2003)
  36. Micheau, Olivier, "The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex", J. Biol. Chem. (United States), 277(47), pp.45162~45171 (2002)
  37. Li, P, "Cytochrome c and dATP-dependent formation of Apaf-1", caspase-9 complex initiates an apoptotic protease cascade, 1997, pp.91(4), 479~489
  38. Chu, Z L, "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis", J. Biol. Chem. (United States), 276(12), pp.9239~9245 (2001)
  39. Alberts B, "Tissues and Cancer in Essential cell biology" (2004), Garland Science
  40. Hebenstreit D, "JAK", STAT-dependent gene regulation by cytokines, 2005, pp.18(4), 243~249
  41. Krainc, D, "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1", J. Biol. Chem. (UNITED STATES), 273(40), pp.26218~26224 (1998)
  42. Wong, M W, "The large subunit of basal transcription factor SNAPc is a Myb domain protein that interacts with Oct-1", Mol. Cell. Biol. (UNITED STATES), 18(1), pp.368~377 (1998)
  43. Zhao Y, "Cancer resistance in transgenic mice expressing the SAC module of Par-4", Cancer Res, 67(19), pp.9276~9285 (2007)
  44. Roussigne, Myriam, "THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies", Oncogene (England), 22(16), pp.2432~2442 (2003)
  45. Rottmann S, "Inhibition of apoptosis by MAD1 is mediated by repression of the PTEN tumor suppressor gene", FASEB J, 22(4), pp.1124~1134 (2008)
  46. Rismanchi N, "STAM adaptor proteins interact with COPII complexes and function in ER-to-Golgi trafficking", Traffic, 10(2), pp.201~217 (2009)
  47. Zhou Q, "ERK signaling is a central regulator for BMP-4 dependent capillary sprouting", Cardiovasc Res, 76(3), pp.390~399 (2007)
  48. Skulachev VP, "Cytochrome c in the apoptotic and antioxidant cascades", FEBS Lett, 423(3), pp.275~280 (1998)
  49. Liu X, "Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c", Cell, 86(1), pp.147~157 (1996)
  50. Lazarow PB, "Biogenesis of peroxisomes", Annu. Rev. Cell Biol, 1, pp.489~530 (1985)
  51. Grou CP, "Properties of the ubiquitin-pex5p thiol ester conjugate", J Biol Chem, 284(16), pp.10504~10513 (2009)
  52. Kang, D E, "Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway", J. Neurosci. (UNITED STATES), 19(11), pp.4229~4237 (1999)
  53. Shav-Tal Y, "PSF and p54(nrb)", NonO--multi-functional nuclear proteins, 2002, pp.531(2), 109~114
  54. Muniyappa H, "Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism", Cell Signal, 20(4), pp.675~683 (2008)
  55. Chakraborty K, "cAMP stringently regulates human cathelicidin antimicrobial peptide expression in the mucosal epithelial cells by activating cAMP-response elementbinding protein, AP-1, and inducible cAMP early repressor", J Biol Chem, 284(33), pp.21810~21827 (2009)

관련 논문AI추천

이 간행물의 다른 논문 (17건)