Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Heptelidic Acid, a Sesquiterpene Lactone, Inhibits Etoposide-Induced Apoptosis in Human Leukemia U937 Cells

  • Kim, Jin-Hee (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Lee, Choong-Hwan (Department of Bioscience and Biotechnology, Konkuk University)
  • Published : 2009.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

In the course of screening for substances that inhibit etoposide (10 ${\mu}g$/ml)-induced apoptosis in human leukemia U937 cells, fungal strain F000120, which exhibits potent inhibitory activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak $C_{18}$ column chromatography and HPLC, and was identified as heptelidic acid (koningic acid) by spectroscopic methods. This compound inhibited caspase-3 induction in U937 cells with an $IC_{50}$ value of 40 ${\mu}M$ after 8 h of etoposide treatment. Fluorescent dye staining with acridine orange and ethidium bromide showed that heptelidic acid inhibited apoptosis. Furthermore, it was found that DNA fragmentation and caspase-3 activation, the biological hallmarks of apoptosis, were inhibited by the compound in a dose-dependent manner, suggesting that heptelidic acid inhibits etoposide-induced apoptosis via downregulation of caspases.

Keywords

References

  1. Agrawal, S., M. L. Agarwal, M. Chatterjee-Kishore, G. R. Stark, and G. M. Chisolm. 2002. Stat1-dependent, p53-independent expression of p21(waf1) modulates oxysterol-induced apoptosis. Mol. Cell Biol. 22: 1981-1992 https://doi.org/10.1128/MCB.22.7.1981-1992.2002
  2. Budihardjo, I., H. Oliver, M. Lutter, X. Luo, and X. Wang. 1999. Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15: 269-290 https://doi.org/10.1146/annurev.cellbio.15.1.269
  3. Ching, J. C., N. L. Jones, P. J. Ceponis, M. A. Karmali, and P. M. Sherman. 2002. Escherichia coli Shiga-like toxins induce apoptosis and cleavage of poly (ADP-ribose) polymerase via in vitro activation of caspases. Infect. Immun. 70: 4669-4677 https://doi.org/10.1128/IAI.70.8.4669-4677.2002
  4. Dove, A. 2001. Making a living out of the art of dying. Nat. Biotechnol. 19: 615-619 https://doi.org/10.1038/90207
  5. Endo, A., K. Hasumi, K. Sakai, and T. Kanbe. 1985. Specific inhibition of glyceraldehyde-3-phosphate dehydrogenase by koningic acid (heptelidic acid). J. Antibiot. (Tokyo) 38: 920-925 https://doi.org/10.7164/antibiotics.38.920
  6. 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
  7. 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
  8. Hanahan, D. and J. Folkman. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364 https://doi.org/10.1016/S0092-8674(00)80108-7
  9. Itoh, Y., K. Kodama, K. Furuya, S. Takahashi, T. Haneishi, Y. Takiguchi, and M. Arai. 1980. A new sesquiterpene antibiotic, heptelidic acid: Producing organisms, fermentation, isolation and characterization. J. Antibiot. (Tokyo) 33: 468-473 https://doi.org/10.7164/antibiotics.33.468
  10. 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
  11. 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. (Tokyo) 50: 370-372 https://doi.org/10.7164/antibiotics.50.370
  12. Lakka, S. S., C. S. Gondi, N. Yanamandra, W. C. Olivero, D. H. Dinh, M. Gujrati, and J. S. Rao. 2004. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene 23: 4681-4689 https://doi.org/10.1038/sj.onc.1207616
  13. Maulik, N. and D. K. Das. 2002. Redox signaling in vascular angiogenesis. Free Radic. Biol. Med. 33: 1047-1060 https://doi.org/10.1016/S0891-5849(02)01005-5
  14. Meier, P. and G. Evan. 1998. Dying like flies. Cell 95: 295- 298 https://doi.org/10.1016/S0092-8674(00)81760-2
  15. 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
  16. Nakazawa, M., T. Uehara, and Y. Nomura. 1997. Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase inhibitor)- induced fragmentation and condensation of DNA in NG108-15 cells. J. Neurochem. 68: 2493-2499 https://doi.org/10.1046/j.1471-4159.1997.68062493.x
  17. Pieper, A. A., A. Verma, J. Zhang, and S. H. Snyder. 1999. Poly (ADP-ribose) polymerase, nitric oxide and cell death. Trends Pharmacol. Sci. 20: 171-181 https://doi.org/10.1016/S0165-6147(99)01292-4
  18. Tanaka, Y., K. Shiomi, K. Kamei, M. Sugoh-Hagino, Y. Enomoto, F. Fang, et al. 1998. Antimalarial activity of radicicol, heptelidic acid and other fungal etabolites. J. Antibiot. (Tokyo) 51: 153- 160 https://doi.org/10.7164/antibiotics.51.153
  19. Ujibe, M., S. Kanno, Y. Osanai, K. Koiwai, T. Ohtake, K. Kimura, K. Uwai, M. Takeshita, and M. Ishikawa. 2005. Octylcaffeate induced apoptosis in human leukemia U937 cells. Biol. Pharm. Bull. 28: 2338-2341 https://doi.org/10.1248/bpb.28.2338
  20. Webster, K. A. 2003. Therapeutic angiogenesis: A complex problem requiring a sophisticated approach. Cardiovasc. Toxicol. 3: 283-298 https://doi.org/10.1385/CT:3:3:283
  21. Woo, M., R. Hakem, M. S. Soengas, G. S. Duncan, A. Shahinian, D. Kagi, et al. 1998. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 12: 806-819 https://doi.org/10.1101/gad.12.6.806
  22. Yadavilli, S. and P. M. Muganda. 2004. Diepoxybutane induces caspase and p53-mediated apoptosis in human lymphoblasts. Toxicol. Appl. Pharmacol. 195: 154-165 https://doi.org/10.1016/j.taap.2003.11.006
  23. Zimmermann, K. C., C. Bonzon, and D. R. Green. 2001. The machinery of programmed cell death. Pharmacol. Ther. 92: 57- 70 https://doi.org/10.1016/S0163-7258(01)00159-0
  24. Zychlinsky, A. 1993. Programmed cell death in infectious diseases. Trends Microbiol. 1: 114-117 https://doi.org/10.1016/0966-842X(93)90118-B

Cited by

  1. Natural sesquiterpenoids vol.27, pp.11, 2009, https://doi.org/10.1039/c0np00007h