Download PDF
Planta Med 2002; 68(3): 198-203
DOI: 10.1055/s-2002-23142
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Mitochondrial Destabilisation and Caspase-3 Activation are Involved in the Apoptosis of Jurkat Cells Induced by Gaudichaudione A, a Cytotoxic Xanthone

Xiaohua Wu1 , Shugeng Cao2 , Sweehock Goh3 , Anne Hsu1 , Benny K. H. Tan1
  • 1Department of Pharmacology, Faculty of Medicine and Science, National University of Singapore, Singapore
  • 2Centre for Natural Product Research, Institute of Molecular and Cell Biology, National University of
    Singapore, Singapore
  • 3Department of Chemistry, Faculty of Science, National University of Singapore, Singapore
Further Information

Publication History

April 27, 2001

September 16, 2001

Publication Date:
25 March 2002 (online)

    Permissions and Reprints

Abstract

Gaudichaudione A, a cytotoxic xanthone obtained from Garcinia gaudichaudii, displayed strong growth inhibitory effects against Jurkat human leukemic cells, parental murine leukemic P388 and P388/DOX-resistant cell lines, and exhibited similar cytotoxicity against P388/DOX as well as P388, but was less toxic toward normal human Chang liver cells. A variety of apoptotic events induced by gaudichaudione A at the mitochondrial and nuclear levels has been characterized. It appears that gaudichaudione A induced a collapse of the mitochondrial transmembrane potential. Caspase-3 was activated and induced internucleosomal DNA fragmentation and externalization of PS residues. The apoptotic features were also observed in ultrastructural studies.

Abbreviations

ΔΨm:mitochondrial transmembrane potential

Ac-DEVD-AMC:N-acetyl-Asp-Glu-Val-Asp-AMC
(7-amino-4-methylcoumarin)

Ac-DEVD-CHO:N-acetyl-Asp-Glu-Val-Asp-CHO (aldehyde)

Apo 2.7:anti-7A6

CCCP:carbonyl cyanide-m-chlorophenylhydrazone

DiOC6(3):3,3′-dihexyloxacarbocyanine iodide

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-
trazolium bromide

Key words

Gaudichaudione A - flow cytometry - apoptosis - caspases - mitochondrial transmembrane potential - annexin V

References

  • 1 Yoon Y, Kim Y O, Lim N Y, Leon W Y, Sung H J. Shikonin, An ingredient of Lithospermum erythrorhizon induced apoptosis in HL60 human premyelocytic leukemia cell line.  Planta Medica. 1999;  65 532-5
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Kim J A, Kang Y S, Jung M W, Lee S H, Lee Y S. Involvement of Ca2+ influx in the mechanism of tamoxifen-induced apoptosis in HepG2 human hepatoblastoma cells.  Cancer Letters. 1999;  147 115-23
    CrossrefPubMedGoogle Scholar
  • 3 Thompson C B. Apoptosis in the pathogenesis and treatment of disease.  Science. 1995;  267 1456-62
    CrossrefPubMedGoogle Scholar
  • 4 Kroemer G, Zamzami N, Susin S A. Mitochondrial control of apoptosis.  Today. 1997;  18 44-51
    PubMedGoogle Scholar
  • 5 Lazebnik Y A, Kaufmann S H, Desnoyers S, Poirier G G, Earnshaw W C. Cleavage of poly(ADP-ribose)polymerase by a protease with properties like ICE.  Nature. 1994;  371 346-7
    CrossrefPubMedGoogle Scholar
  • 6 Tewari M, Quan L T, O’Rourke K, Desnoyers S, Zeng Z, Beidler D R, Poirier G G, Salvesen G S, Salvesen V M, Dixit Y. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase.  Cell. 1995;  81 801-9
    CrossrefPubMedGoogle Scholar
  • 7 Janicke R U, Sprengart M L, Wati M R, Porter A G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis.  J. Biol. Chem.. 1998;  273 9357-60
    CrossrefPubMedGoogle Scholar
  • 8 Parter A G, Janicke R U. Emerging roles of caspase-3 in apoptosis.  Cell Death Different.. 1999;  6 99-104
    PubMedGoogle Scholar
  • 9 Clement M V, Hirpara J L, Chawdhury S H, Pervaiz S. Chemopreventive agent resveratrol, a natural product derived from grape, triggers CD95 signaling-dependent apoptosis in human tumor cells.  Blood. 1998;  92 996-1002
    CrossrefPubMedGoogle Scholar
  • 10 Asano J, Chiba K, Tada M, Yoshii T. Cytotoxic xanthones from Garcinia hanburyi .  Phytochemistry. 1996;  41 815-20
    CrossrefPubMedGoogle Scholar
  • 11 Bennett G J, Lee H H. Xanthones from Guttiferae.  Phytochemistry. 1989;  28 967-98
    CrossrefPubMedGoogle Scholar
  • 12 Cao S G, Wu X H, Tan B KH, Goh S H. Cytotoxic caged tetraprenylated xanthonoids from Garcinia gaudichaudii (Guttiferae).  Tetrahedron Letters. 1998;  39 3353-6
    CrossrefPubMedGoogle Scholar
  • 13 Liu Q Y, Tan B KH. Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines.  Life Sciences.. 2000;  67 1207-18
    CrossrefPubMedGoogle Scholar
  • 14 Zhang C H, Ao Z H, Seth A, Schlossman S F. A mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells.  Journal of Immunology. 1996;  157 3980-7
    PubMedGoogle Scholar
  • 15 Janicke R U, Sprengart M L, Wati M R, Porter A G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis.  J. Biol. Chem.. 1998;  273 9375-80
    PubMedGoogle Scholar
  • 16 Woo M, Hakem R, Soengas M S, Duncan G S, Shahinian A, Kagi D, Hakem A, McCurrach M, Khoo W, Kaufman S A, Senaldi G, Howard T, Lowe S W, Mak T W. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.  Genes and Development. 1998;  12 806-19
    PubMedGoogle Scholar
  • 17 Kroemer G, Dallaporta B, Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis.  Annu. Rev. Physiol.. 1998;  60 619-42
    CrossrefPubMedGoogle Scholar
  • 18 Bernard P, Petronilli V. The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal.  J. Bioenerg. Biomembr.. 1996;  28 129-36
    PubMedGoogle Scholar

Dr. Benny K. H. Tan,Associate Professor 

Department of Pharmacology

National University of Singapore


10 Kent Ridge Crescent

Singapore 119260

Email: phctankh@nus.edu.sg

Phone: (65) 874 3272

Fax: (65) 773 0579

      >