[en] Background: Trachylobane diterpenes are secondary metabolites quite rare in nature and their bioactivities are poorly known. Recently we have described the cytotoxic activity of ent- trachyloban-3‚-ol isolated from the leaves of Croton zambesicus, a plant used in African folk medicine. Materials and Methods: Cell viability on several cell lines, cell morphology, DNA laddering, annexin V and caspase-3 activation experiments were undertaken in order to analyse the cytotoxicty of trachylobane diterpene and to determine if this compound is able to induce apoptosis. Results: ent-trachyloban-3‚-ol exerts a dose-dependent cytotoxic effect and which varies between cell lines. Induction of apoptosis in HL-60 cells could be detected at a concentration of 50 ÌM after 24-h treatment. Conclusion: We show here, for the first time, that a trachylobane diterpene is able to induce apoptosis in human promyelocytic leukemia cells via caspase-3 activation in a concentration-dependent manner.
Disciplines :
Oncology
Author, co-author :
Block, Sébastien; Université Catholique de Louvain - UCL > Unité d'Analyse Chimique et Physico Chimique des Médicaments
Gerkens, Pascal; Université de Liège - ULiège > Histologie et Cytologie
Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Jolois, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Mingeot-Leclercq, Marie-Paule; Université Catholique de Louvain - UCL > Unité de Pharmacologie Cellulaire et Moléculaire
De Pauw-Gillet, Marie-Claire ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie - Département des sciences biomédicales et précliniques
Quetin-Leclercq, Joëlle; Université Catholique de Louvain - UCL > Unité d’Analyse Chimique et Physico-Chimique des Médicaments
Language :
English
Title :
Induction of Apoptosis in Human Promyelocytic Leukemia Cells by a Natural Trachylobane Diterpene
Block S, Stévigny C, De Pauw-Gillet M-C, de Hoffmann E, Llabrès G, Adjakidjé V and Quetin-Leclercq J: em-Trachyloban- 3β-ol a new cytotoxic diterpene from Croton zambesicus. Planta Medica 68: 647-649, 2002.
Watt JM and Breyer-Brandwikj MG: The Medicinal and Poisonous Plants of Southern and Eastern Africa. 2nd edition, 1962. E. and S. Livingstone Ltd., London, UK.
Hugel G, Lods L, Mellor JM, Theobald DW and Ourisson G: Diterpènes de Trachylobium. I.- Introduction générale. Isolement de kauranol et de huit diterpènes nouveaux. Bulletin de la Société Chimique de France: 2882-2887, 1965.
Hugel G, Lods L, Mellor JM, Theobald DW and Ourisson G: Diterpènes de Trachylobium. II.- Structure des diterpènes tétraet pentacycliques de Trachylobium. Bulletin de la Société Chimique de France: 2888-2894, 1965.
Fraga BM: The trachylobane diterpenes. Phytochem Anal 5: 49-56, 1994.
Zgoda-Pols JR, Freyer AA, Kilmer L and Porter JR: Antimicrobial diterpenes from the stem bark of Mitrephora celebica. Fitoterapia 73: 434-438, 2002.
McCesney JD, Clark AM and Silveira ER: Antimicrobial diterpenes of Croton sonderianus, 1. Hardwickic and 3,4-secotrachylobanoic acids. J Nat Prod 54: 1625-1633, 1991.
Nakano M, Fukushima M and Azuma H: Isolation and chemical characterization of antimicrobial compounds from sunflower (Helianthus onnus L.). Shokuhin Eiseigaku Zasshi 36: 22-28, 1995.
Mitsher LA, Rao GSR, Veysoglu T, Drake S and Haas T: Isolation and identification of trachyloban-19-oic and (-)-kaur-16-en-19-oic acids as antimicrobial agents from the prairie sunflower, Helianthus annuus. J Nat Prod 46: 745-746, 1983.
Daniewski WM, Skibicki P, Bloszyk E, Budesinsky M and Holub M: Constituents of Helianthus mollis and their antifeedant activity. Polish J Chem 67: 1255-1259, 1993.
Mullin CA, Alfatafta AA, Harman JL, Everett SL and Serino AA: Feeding and toxic effects of floral sesquiterpene lactones, diterpenes and phenolics from sunflower (Helianthus annuus L.) on western corn rootworm. J Agr Food Chem 39: 2293-2299, 1991.
Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Meth 65: 55-63, 1983.
Stévigny C, Block S, De Pauw-Gillet MC, de Hoffmann E, Llabrès G, Adjakidjé V and Quetin-Leclercq J: Cytotoxic aporphine alkaloids from Cassytha filiformis. Planta Medica 68: 1042-1044, 2002.
Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M and Lazebnik YA: Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376: 37-43, 1995.
Bertrand R, Solary E, Jenkins J and Pommier Y: Apoptosis and its modulation in human promyelocytic HL-60 cells treated with DNA topoisomerase I and II inhibitors. Exp Cell Res 207: 388-397, 1993.
Kerr JFR, Wyllie AH and Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implication in tissue kinetics. Br J Cancer 26: 239-257, 1972.
Wyllie AH: Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555-556, 1980.
Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, Van Schie RC, LaFace DM and Green DR: Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182: 1546-1556, 1995.
Raynal P and Pollard HB: Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium and phospholipid-binding proteins. Biochimica et Biophysica Acta 1197: 63-93, 1994.
Kidd V: Proteolytic activities that mediate apoptosis. Ann Rev Physiol 60: 533-573, 1998.
Nunez G, Benedict M, Hu Y and Inohara N: Caspases: the proteases of the apoptotic pathway. Oncogene 12: 3237-3245, 1998.
Kauffman SH: Cell death induced by topoisomerase-targeted drugs: more questions than answers. Biochem Biophys Acta 1400: 195-211, 1998.
Shimizu T and Pommier Y: Camptothecin-induced apoptosis in p-53 null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichlororisocoumarin suggest an involvement of both caspases and serine proteases. Leukemia 11: 1238-1244, 1997.
Qing C, Jiang C, Zhang JS and Ding J: Induction of apoptosis in human leukemia K-562 and gastric carcinoma SGC-7901 cells by salvicine, a novel anticancer compound. Anti-Cancer Drugs 12: 51-56,2001.
Gu WZ, Chen R, Brandwein S, McAlpine J and Burres N: Isolation, purification, and characterization of immunosuppressive compounds from Tripterygium: triptolide and tripdiolide. Int J Immunopharmacol 17: 351-356, 1995.
Yang SX, Gao HL, Xie SS, Zhang WR and Long ZZ: Immunosuppression of triptolide and its effect on skin allograft survival. Int J Immunopharmacol 14: 963-969, 1992.
Dai D, Musser JH and Lennox ES: Triptolide derivatives for modulation of apoptosis and immunosuppression. PCT Int. Appl. 2003 CODEN: PIXXD2 WO 2003101951 A2 20031211.