Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Rengyolone Inhibits Apoptosis via Etoposide-Induced Caspase Downregulation

  • Kim, Jin-Hee (Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Choong-Hwan (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2008.04.04
  • Accepted : 2008.07.30
  • Published : 2009.03.31
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Abstract

In the course of screening for substances inhibiting apoptosis of U937 human leukemia cells induced by etoposide ($10\;{\mu}g/ml$), Forsythiae fructus, which showed a high level of inhibition, was selected. The regulating compounds were purified from the ethyl acetate extract by silica gel column chromatography and HPLC. The active substance was purified and identified as rengyolone by spectroscopic methods. This compound showed inhibitory activity on caspase-3 induction, a major protease of the apoptosis cascade, with an $IC_{50}$ value of $38.96\;{\mu}M$ after 8 h of etoposide treatment in U937 cells. The expression level of caspase-3 and poly(ADP-ribose) polymerase (PARP) were dose-dependently inhibited by the compound, suggesting that rengyolone inhibits etoposide-induced apoptosis via downregulation of caspases.

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References

  1. Alfaro, C., A. Urios, M. C. Gonzalez, P. Moya, and M. Blanco. 2003. Screening for metabolites from Penicillium novae-zeelandiae displaying radical-scavenging activity and oxidative mutagenicity:Isolation of gentisyl alcohol. Mutat. Res. 539: 187-194 https://doi.org/10.1016/S1383-5718(03)00166-9
  2. Bae, M. A., K. Yamada, D. Uemura, J. H. Seu, and Y. H. Kim. 1998. Aburnatubolactam C, a novel apoptosis-inducing substance produced by marine Streptomyces sp. SCRC A-20. J. Microbiol. Biotechnol. 8: 455-460
  3. Bhunia, A. K. and X. Feng. 1999. Examination of cytopathic effect and apoptosis in Listeria monocytogenes-infected hybridoma B-lymphocyte (Ped-2E9) line in vitro. J. Microbiol. Biotechnol. 9: 398-403
  4. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  5. Cavalieri, E., S. Mariotto, C. Fabrizi, A. C. Prati, R. Gottardo, S. Leone, et al. 2004. $\alpha$-Bisabolol, a nontoxic natural compound, strongly induces apoptosis in glioma cells. Biochem. Biophys. Res. Commun. 315: 589-594 https://doi.org/10.1016/j.bbrc.2004.01.088
  6. Dove, A. 2001. Making a living out of the art of dying. Nat. Biotechnol. 19: 615-619 https://doi.org/10.1038/90207
  7. Endo, K., K. Seya, and H. Hikino. 1989. Biogenesis-like transformation of salidroside to rengyol and its related cyclohexyletanoids of Forsythia suspensa. Tetrahedron 45: 3673-3682 https://doi.org/10.1016/S0040-4020(01)89229-2
  8. Fernandes-Alnemri, T., G. Litwack, and E. S. Alnemri. 1994. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J. Biol. Chem. 269: 30761-30764
  9. Goodwin, C. J., S. J. Holt, S. Downes, and N. J. Marshall. 1995. Microculture tetrazolium assays: A comparison between two new tetrazolium salts, XTT and MTS. J. Immunol. Methods 179: 95-103 https://doi.org/10.1016/0022-1759(94)00277-4
  10. Guo, Y. and N. Kyprianou. 1999. Restoration of transforming growth factor beta signaling pathway in human prostate cancer cells suppresses tumorigenicity via induction of caspase-1-mediated apoptosis. Cancer Res. 59: 1366-1371
  11. Gurtu, V., S. R. Kain, and G. Zhang. 1997. Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal. Biochem. 251: 98-102 https://doi.org/10.1006/abio.1997.2220
  12. Ishikawa, Y., K. Morimoto, and T. Hamasaki. 1986. Gentisyl alcohol produced by Penicillium commune, a potent antioxidant and synergist for tocopherol. J. Jpn. Oil Chem. Soc. 35: 13-16
  13. Jensen, S$\phi$ren R., H. Franzyk, E. Wallander. 2002. Chemotaxonomy of the Oleaceae: Iridoids as taxonomic markers. Phytochemistry 60: 213-231 https://doi.org/10.1016/S0031-9422(02)00102-4
  14. Jeong, Y. O., K. S. Kim, J. Y. Oh, J. C. Park, J. H. Bang, S. W. Choi, and J. C. Lee. 2003. Growth inhibition and apoptosis induction of gastric cancer cells by copper glycinate complex. J. Microbiol. Biotechnol. 13: 394-399
  15. Ji, L., G. Zhang, and Y. Hirabayashi. 1995. Inhibition of tumor necrosis factor alpha- and ceramide-induced internucleosomal DNA fragmentation by herbimycin A in U937 cells. Biochem. Biophys. Res. Commun. 212: 640-647 https://doi.org/10.1006/bbrc.1995.2017
  16. Kakeya, H., H. P. Zhang, K. Kobinata, R. Onose, C. Onozawa, T. Kudo, and H. Osada. 1997. Cytotrienin A, a novel apoptosis inducer in human leukemia HL-60 cells. J. Antibiot. 50: 370-372 https://doi.org/10.7164/antibiotics.50.370
  17. Kim, J. W., H. Adachi, K. Shin-ya, Y. Hayakawa, and H. Seto. 1997. Apoptolidin, a new apoptosis inducer in transformed cells from Nocardiopsis sp. J. Antibiot. 50: 628-630 https://doi.org/10.7164/antibiotics.50.628
  18. Kim, J. H., D. H. Kim, S. H. Baek, H. J. Lee, M. R. Kim, H. J. Kwon, and C. H. Lee. 2006. Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by downregulation of NF-$\kappa$B and p38 MAP kinase activity in LPSstimulated RAW 264.7 cells. Biochem. Pharmacol. 51: 383-394 https://doi.org/10.1016/0006-2952(95)02099-3
  19. Kim, N. Y., T. H. Kang, E. K. Song, H. O. Pae, H. T. Chung, and Y. C. Kim. 2000. Inhibitory effects of butanol fraction of the aqueous extract of Forsythia koreana on the nitric oxide production by murine macrophage-like RAW 264.7 cells. J. Ethnopharmacol. 73: 323-327 https://doi.org/10.1016/S0378-8741(00)00298-1
  20. Kitagawa, S., H. Tsukamoto, S. Hisada, and S. Nishibe. 1984. Studies on the Chinese crude drug Forsythiae fructus. Chem. Pharm. Bull. 32: 1209-1213 https://doi.org/10.1248/cpb.32.1209
  21. Lee, C. H., J. H. Kim, H. J. Lee, and Y. H. Kho. 2001. Two new constituents of Isodon excisus and their evaluation in an apoptosis inhibition assay. J. Nat. Prod. 64: 659-660 https://doi.org/10.1021/np000604g
  22. Lee, C. H., M. A. Lee, Y. H. Cho, H. Y. Lim, K. H. Kim, and Y. H. Lim. 2001. In vitro detection of apoptosis in human promyelocytic leukemia HL-60 cells by $1_{H}$-NMR. J. Microbiol. Biotechnol. 11: 539-542
  23. Meier, P. and G. Evan. 1998. Dying like flies. Cell 95: 295-298 https://doi.org/10.1016/S0092-8674(00)81760-2
  24. Miura, M., H. Zhu, R. Rotello, E. A. Hartwieg, and J. Yuan. 1993. Induction of apoptosis in fibroblasts by IL-1 $\beta$-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75: 653-660 https://doi.org/10.1016/0092-8674(93)90486-A
  25. Nicholson, D. W., A. Ali, N. A. Thornberry, J. P. Vaillancourt, C. K. Ding, M. Gallant, et al. 1995. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376: 37-43 https://doi.org/10.1038/376037a0
  26. Steller, H. 1995. Mechanisms and genes of cellular suicide. Science 267: 1445-1449 https://doi.org/10.1126/science.7878463
  27. Wiley, S. R., K. Schooley, P. J. Smolak, W. S. Din, C. P. Huang, J. K. Nicholl, et al. 1995. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3: 673-682 https://doi.org/10.1016/1074-7613(95)90057-8
  28. Yamashita, N., K. Shin-ya, K. Furihata, Y. Hayakawa, and H. Seto. 1998. New ravidomycin analogues, FE35A and FE35B, apoptosis inducers produced by Streptomyces rochei. J. Antibiot. 51: 1105-1108 https://doi.org/10.7164/antibiotics.51.1105

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