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Biotechnology and Bioprocess Engineering

, Volume 15, Issue 1, pp 167–172 | Cite as

Widdrol from Juniperus chinensis induces apoptosis in human colon adenocarcinoma HT29 Cells

  • Hyun-Ju Kwon
  • Eun-Woo Lee
  • Yun-Kyung Hong
  • Hee-Jung Yun
  • Byung-Woo KimEmail author
Articles

Abstract

Juniperus chinensis is a well-known folk remedy in Korea, shown to exhibit anti-tumor, anti-bacterial, anti-fungal, abortifacient, anti-platelet, vasorelaxing, and anti-viral activities. In this study, we report the cytotoxic activity as well as the apoptotic mechanism of widdrol extracted from Juniperus chinensis against the human colon adenocarcinoma cell line HT29. Treatment of HT29 cells with various concentrations of widdrol inhibited growth and induced apoptosis in a dose-dependent manner, as determined by cell viability, chromatin condensation, and sub-G1 phase accumulation. Western blot analysis revealed that apoptosis of HT29 cells was associated with release of cytochrome C from mitochondria into the cytosol, activation of caspases-3, -8, and -9, and proteolytic cleavage of PARP. These results suggest that widdrol exhibits an anti-proliferative effect on HT29 cells via apoptosis and can be a potential candidate in the field of anti-cancer drug discovery.

Keywords

plant widdrol Juniperus chinensis apoptosis HT29 cell anti-cancer anti-proliferative activity 

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References

  1. 1.
    Kaufmann, S. H. and M. O. Hengartner (2001) Programmed cell death: alive and well in the new millennium. Trends Cell Biol. 11: 526–534.CrossRefGoogle Scholar
  2. 2.
    Kaufmann, S. H. and W. C. Earnshaw (2000) Induction of apoptosis by cancer chemotherapy. Exp. Cell Res. 256: 42–49.CrossRefGoogle Scholar
  3. 3.
    Salvesen, G. S. and V. M. Dixit (1997) Caspases: intracellular signaling by proteolysis. Cell 91: 443–446.CrossRefGoogle Scholar
  4. 4.
    Shi, Y. (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol. Cell 9: 459–470.CrossRefGoogle Scholar
  5. 5.
    Denecker, G., D. Vercammen, W. Declercq, and P. Vandenabeele (2001) Apoptotic and necrotic cell death induced by death domain receptors. Cell Mol. Life Sci. 58: 356–370.CrossRefGoogle Scholar
  6. 6.
    Wilson, S. E. (1999) Stimulus-specific and cell typespecific cascades: emerging principles relating to control of apoptosis in the eye. Exp. Eye Res. 69: 255–266.CrossRefGoogle Scholar
  7. 7.
    Kelekar, A. and C. B. Thompson (1998) Bcl-2 family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol. 8: 324–330.CrossRefGoogle Scholar
  8. 8.
    Newmeyer, D. D. and S. Ferguson-Miller (2003) Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112: 481–490.CrossRefGoogle Scholar
  9. 9.
    Chandra, J., A. Samali, and S. Orrenius (2000) Triggering and modulation of apoptosis by oxidative stress. Free Rad. Biol. Med. 29: 323–333.CrossRefGoogle Scholar
  10. 10.
    Germain, M., E. B. Affar, D. D’Amours, V. M. Dixit, G. S. Salvesen, and G. G. Poirier (1999) Cleavage of automodified poly (ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J. Biol. Chem. 274: 28379–28384.CrossRefGoogle Scholar
  11. 11.
    Dirr, M. A. (1977) Manual of woody landscape plants: their identification, ornamental characteristics, culture, propagation, and uses. 4th ed., p. 1007. Stipes Publishing Company, Champaign, IL, USA.Google Scholar
  12. 12.
    Corner, E. J. H. (1988) Wayside Trees of Malaya. 3rd ed., pp. 396–446. Malayan Nature Society, Kuala Lumpur, Malaysia.Google Scholar
  13. 13.
    Kuo, Y. H. and W. C. Chen (1994) Three new diterpenes, 1,3-dioxototarol, isototarolenone, and 1-oxo-3β-hydroxytotarol from the roots of Juniperus chine-nsis Linn. Chem. Pharm. Bull. 42: 1774–1776.Google Scholar
  14. 14.
    Perry, L. M. (1980) Medicinal Plants of East and Southeast Asia. pp. 240–241. MIT Press, Cambridge, MA, USA.Google Scholar
  15. 15.
    Ohashi, H., T. Asai, and S. Kawai (1994) Screening of main Japanese conifers for antifungal leaf components, sesquiterpenes of Juniperus chinensis var. pyramidalis. Holzforschung 48: 193–198.CrossRefGoogle Scholar
  16. 16.
    Clark, A. M., J. D. McChesney, and R. P. Adams (1988) Antimicrobial properties of heartwood, bark/sapwood, and leaves of Juniperus species. Phytother. Res. 4: 15–19.CrossRefGoogle Scholar
  17. 17.
    Johnson, A. E., L. F. James, and J. Spiller (1976) The abortifacient and toxic effects of big sagebrush (Artemisia tridentata) and juniper (Juniperus osteosperma) on domestic sheep. J. Range Manag. 29: 278–280.CrossRefGoogle Scholar
  18. 18.
    Appel, A. G. and T. P. Mack (1989) Repellency of milled aromatic eastern red cedar to domiciliary cockroaches (Dictyoptera: Blattellidae and Blattidae). J. Econ. Entomol. 82: 152–155.Google Scholar
  19. 19.
    Agrawal, O. P., S. Bharadwaj, and R. Mathur (1980) Antifertility effects of fruits of Juniperus communis. Planta Med. 32: 98–101.CrossRefGoogle Scholar
  20. 20.
    Teng, C. M., C. H. Lin, Y. H. Kuo, Y. L. Lin, and T. F. Huang (1994) Antiplatelet and vasorelaxing action of the acetoxy derivative of cedranediol isolated from Juniperus squamata. Planta Med. 60: 209–213.CrossRefGoogle Scholar
  21. 21.
    Feliciano, A. S., M. Gordaliza, J. M. M. del-Corral, M. A. Castro, M. D. G. Gravalos, and P. R. Lazaro (1993) Antineoplastic and antiviral activities of some cyclolignans. Planta Med. 59: 246–249.CrossRefGoogle Scholar
  22. 22.
    Tammami, B., S. J. Torrance, and J. R. Cole (1977) Antitumor agent from Juniperus bermudiana (Pinaceae): deoxypodophyllotoxin. Phytochemistry 16: 1100–1101.CrossRefGoogle Scholar
  23. 23.
    Yarelis, O. N., S. S. Iraida, G. C. Isidro, and H. G. Rosario (2006) The antifungal activity of widdrol and its biotransformation by Colletotrichum gloeosporioides (penz.) Penz. & Sacc. and Botrytis cinerea Pers. J. Agric. Food Chem. 54: 7517–7521.CrossRefGoogle Scholar
  24. 24.
    Enzell, C. (1962) The chemistry of the natural order cupressales 47. The structures and absolute configurations of widdrol and widdrol-α-epoxide. Acta Chem. Scand. 16: 1552–1568.Google Scholar
  25. 25.
    Hu, W. and J. J. Kavanagh (2003) Anticancer therapy targeting the apoptotic pathway. Lancet Oncol. 4: 721–729.CrossRefGoogle Scholar
  26. 26.
    Tan, M. L., S. F. Suaiman, N. Najimuddin, M. R. Smian, and T. S. Tengku Muhammad (2005) Methanolic extract of Pereskia bleo(Kunth) DC. (Cactaceae) induces apoptosis in breast carcinama, T47-D cell line. J. Ethnopharmacol. 96: 287–294.CrossRefGoogle Scholar
  27. 27.
    Korsmeyer, S. J., M. C. Wei, M. Saito, S. Weiler, J. Oh, and P. H. Schlesinger (2000) Pro-apoptotic cascade activates BID, which oligomerized BAK or BAX into pores that result in the release of cytochrome C. Cell Death Differ. 7: 1166–1173.CrossRefGoogle Scholar
  28. 28.
    Luo, X., I. Budihardjo, H. Zou, C. Slaughter, and X. Wang (1998) Bid, a Bcl2 interacting protein, mediates cytochrome C release from mitochondria in response to activation of cell death receptors. Cell 94: 481–490.CrossRefGoogle Scholar
  29. 29.
    Liu, X., C. N. Kim, J. Yang, R. Jemmerson, and X. Wang (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome C. Cell 86: 147–157.CrossRefGoogle Scholar
  30. 30.
    Janicke, R. U., M. L. Sprengart, M. R. Wati, and A. G. Porter (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem. 273: 9357–9360.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Hyun-Ju Kwon
    • 1
    • 2
    • 3
  • Eun-Woo Lee
    • 1
    • 3
  • Yun-Kyung Hong
    • 1
  • Hee-Jung Yun
    • 2
  • Byung-Woo Kim
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Life Science and Biotechnology, College of Natural ScienceDongeui UniversityBusanKorea
  2. 2.Department of Biomaterial ControlDongeui University Graduate SchoolBusanKorea
  3. 3.Blue-Bio Industry RICDongeui UniversityBusanKorea

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