Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Gene Expression Profiling Reveals that Paeoniflorin Has an Apoptotic Potential in Human Leukemia U937 Cells

  • Lim, Soo-Hyun (Department of Biochemistry, College of Oriental Medicine, Kyung Hee University) ;
  • Ahn, Kwang-Seok (Department of Oriental Pathology, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Sung-Hoon (Department of Oriental Pathology, College of Oriental Medicine, Kyung Hee University) ;
  • Jang, Hyeung-Jin (Department of Biochemistry, College of Oriental Medicine, Kyung Hee University)
  • Published : 2009.12.31
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Abstract

A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

Keywords

References

  1. Tsuboi, H. et al. Paeoniflorin induces apoptosis of lymphocytes through a redox-linked mechanism. J Cell Biochem 93:162-172 (2004) https://doi.org/10.1002/jcb.20134
  2. Salunga, T. L. et al. Identification of genes responsive to paeoniflorin, a heat shock protein-inducing compound, in human leukemia U937 cells. Int J Hyperthermia 23:529-537 (2007) https://doi.org/10.1080/02656730701639499
  3. Hori, T. et al. Molecular mechanism of apoptosis and gene expressions in human lymphoma U937 cells treated with anisomycin. Chem Biol Interact 172:125-140 (2008) https://doi.org/10.1016/j.cbi.2007.12.003
  4. Jimenez A, V. D. Anisomycin and related antibiotics (ed. E, H. F.) Springer-Verlag, New York (1979)
  5. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J. & Greenberg, M. E. Opposing effects of ERK and JNKp38 MAP kinases on apoptosis. Science 270:1326-1331 (1995) https://doi.org/10.1126/science.270.5240.1326
  6. Zanke, B. W. et al. The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr Biol 6: 606-613 (1996) https://doi.org/10.1016/S0960-9822(02)00547-X
  7. Park, J. et al. Activation of c-Jun N-terminal kinase antagonizes an anti-apoptotic action of Bcl-2. J Biol Chem 272:16725-16728 (1997) https://doi.org/10.1074/jbc.272.27.16725
  8. Ogata, H. et al. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 27, 29-34 (1999) https://doi.org/10.1093/nar/27.1.29
  9. Washida, K., Itoh, Y., Iwashita, T. & Nomoto, K. Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in nara prefecture, Japan. Chem Pharm Bull (Tokyo) 57:971-974 (2009) https://doi.org/10.1248/cpb.57.971
  10. Wu, H., Li, W., Wang, T., Shu, Y. & Liu, P. Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracilinduced apoptosis in human gastric carcinoma cells. Biomed Pharmacother 62:659-666 (2008) https://doi.org/10.1016/j.biopha.2008.08.002
  11. Hung, J. Y., Yang, C. J., Tsai, Y. M., Huang, H. W. & Huang, M. S. Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligandmediated apoptotic pathway in human non-small cell lung cancer A549 cells. Clin Exp Pharmacol Physiol 35:141-147 (2008)
  12. Zhong, S. Z., Ge, Q. H., Li, Q., Qu, R. & Ma, S. P. Peoniflorin attentuates Abeta ((1-42))-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci 280:71-78 (2009) https://doi.org/10.1016/j.jns.2009.01.027
  13. Nizamutdinova, I. T. et al. Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats. Planta Med 74:14-18 (2008) https://doi.org/10.1055/s-2007-993775
  14. Jiang, B., Qiao, J., Yang, Y. & Lu, Y. Inhibitory effect of paeoniflorin on the inflammatory vicious cycle between adipocytes and macrophages. J Cell Biochem (2009) https://doi.org/10.1002/jcb.22173
  15. Zhang, L. L. et al. Paeoniflorin suppresses inflammatory mediator production and regulates G proteincoupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats. Inflamm Res 57:388- 395 (2008) https://doi.org/10.1007/s00011-007-7240-x
  16. Huang, H. et al. A genome-wide microarray analysis reveals anti-inflammatory target genes of paeonol in macrophages. Inflamm Res 57:189-198 (2008) https://doi.org/10.1007/s00011-007-7190-3
  17. Guo, Z., Wang, J., Yang, J., Wu, N. & Zhang, Y. The Role of p53 and p65 in heat shock-induced inhibition of cyclin D1. Biochim Biophys Acta 1789:758-762 (2009) https://doi.org/10.1016/j.bbagrm.2009.09.011
  18. Kulkarni, D. et al. A polymorphic variant in human MDM4 associates with accelerated age of onset of estrogen receptor negative breast cancer. Carcinogenesis 30:1910-1915 (2009) https://doi.org/10.1093/carcin/bgp224
  19. Regina, S. et al. Increased tissue factor expression is associated with reduced survival in non-small cell lung cancer and with mutations of TP53 and PTEN. Clin Chem 55:1834-1842 (2009) https://doi.org/10.1373/clinchem.2009.123695
  20. Feng, Z. et al. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res 67:3043-3053 (2007) https://doi.org/10.1158/0008-5472.CAN-06-4149
  21. Konstantakou, E. G. et al. Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses. Int J Oncol 35:401-416 (2009) https://doi.org/10.3892/ijo_00000353
  22. Chen, H., Xia, Y., Fang, D., Hawke, D. & Lu, Z. Caspase- 10-mediated heat shock protein 90 beta cleavage promotes UVB irradiation-induced cell apoptosis. Mol Cell Biol 29:3657-3664 (2009) https://doi.org/10.1128/MCB.01640-08
  23. Walczak, H. & Haas, T. L. Biochemical analysis of the native TRAIL death-inducing signaling complex. Methods Mol Biol 414:221-239 (2008) https://doi.org/10.1007/978-1-59745-339-4_16
  24. Lamar, J. M., Iyer, V. & DiPersio, C. M. Integrin alpha3beta1 potentiates TGFbeta-mediated induction of MMP-9 in immortalized keratinocytes. J Invest Dermatol 128:575-586 (2008) https://doi.org/10.1038/sj.jid.5701042
  25. Sohn, K. H. et al. Genome wide expression profile of Asiasarum sieboldi in LPS-stimulated BV-2 Microglial Cells. Molecular & Cellular Toxicology 4:205-210 (2008)
  26. Raines, K. W. et al. Nitric oxide inhibition of ERK1 /2 activity in cells expressing neuronal nitric-oxide synthase. J Biol Chem 279:3933-3940 (2004) https://doi.org/10.1074/jbc.M304813200
  27. Sim, S. et al. NADPH oxidase-derived reactive oxygen species-mediated activation of ERK1/2 is required for apoptosis of human neutrophils induced by Entamoeba histolytica. J Immunol 174:4279-4288 (2005)