본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Molecular & cellular toxicology v.3 no.4, 2007년, pp.246 - 253   피인용횟수: 2
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Identification of Marker Genes Related to Cardiovascular Toxicity of Doxorubicin and Daunorubicin in Human Umbilical Vein Endothelial Cells (HUVECs)

Kim, Youn-Jung   (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology  ); Lee, Ha-Eun   (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology  ); Ryu, Jae-Chun   (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology  );
  • 초록

    Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.


  • 주제어

    Doxorubicin .   Daunorubicin .   Cardiovascular toxicity .   HUVECs .   Apoptosis.  

  • 참고문헌 (20)

    1. Kalyanaraman, B. et al. Doxorubicin-induced apoptosis: implications in cardiotoxicity. Mol Cell Biochem 234/235:119-124 (2002) 
    2. Kim, Y. J., Chai, Y. G. & Ryu, J. C. Selenoprotein W as molecular target of methylmercury in human neuronal cells is down-regulated by GSH depletion. Biochem Biophys Res Commun 30:1095-1102 (2005) 
    3. Kim, Y. J., Kim, M. S. & Ryu, J. C. Genotoxicity and identification of differentially expressed genes of formaldehyde in human Jurkat cells. Mol Cell Toxicol 1:230-236 (2005)     
    4. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63 (1983) 
    5. Frei, K. et al. Ex vivo malignant glioma cells are sensitive to Fas (CD95/APO-1) ligand-mediated apoptosis. J Neuroimmunol 87:105-113(1998) 
    6. Han, J. W. et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci USA 20:11318-11323 (2001) 
    7. Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121 (2001) 
    8. Araki, W. & Wurtman, R. J. Increased expression of amyloid precursor protein and amyloid precursor-like protein 2 during trophic factor withdrawal-induced death of neuronal PC12 cells. Brain Res Mol Brain Res 56:169-177 (1998) 
    9. Mordente, A. et al. Human heart cytosolic reductases and anthracycline cardiotoxicity. IUBMB Life 52:83-88 (2001) 
    10. Wei, J. S. et al. BBC3 mediates fenretinide-induced cell death in neuroblastoma. Oncogene 54:7976-7983 (2005) 
    11. Barry, E. et al. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin Pharmacother 8:1039-1058 (2007) 
    12. Elliott, P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol 33(3 suppl 8):S2-S7 (2006) 
    13. Devalapally, H. et al. Beta-galactoside prodrugs of doxorubicin for application in antibody directed enzy-me prodrug therapy/prodrug monotherapy. Arch Pharm Res 6:723-732 (2007)     
    14. Grant, D. S., Williams, T. L., Zahaczewsky, M. & Dicker, A. P. Comparison of antiangiogenic activities using paclitaxel (Taxol) and docetaxel (Taxotere). Int J Cancer 104:121-129 (2002) 
    15. Ryu, J. C. et al. Promising next generation technology in toxicology-toxicogenomics. Mol Cell Toxicol 1:1-6 (2005)     
    16. Lee, J. H., Lee, J. H., Rho, S. B. & Chun, T. Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPK1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett 14:1011-1015 (2005) 
    17. Lum, H. & Roebuck, K. A. Oxidant stress and endothelial dysfunction. Am J Physiol 280:C719-C741 (2001) 
    18. Nathalie, C. et al. Fas ligand is localized to membrane raft, where it displays increased cell death-inducin activity. Blood 6:2384-2391 (2006) 
    19. Singal, P. K. et al. Adriamycin-induced heart failure: mechanism and modulation. Mol Cell Biochem 207: 77-85 (2000) 
    20. Tang, X., Milyavsky, M., Goldfinger, N. & Rotter, V. Amyloid-beta precursor-like protein APLP1 is a novel p53 transcriptional target gene that augments neuroblastoma cell death upon genotoxic stress. Oncogene in press (2007) 
  • 이 논문을 인용한 문헌 (2)

    1. 2008. "" Molecular & cellular toxicology, 4(1): 45~51     
    2. 2009. "" Molecular & cellular toxicology, 5(2): 113~119     

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • NDSL :
유료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기