Planta Med 2003; 69(8): 701-704
DOI: 10.1055/s-2003-42789
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Anti-Tumour Activity of Digitalis purpurea L. subsp. heywoodii

Miguel López-Lázaro1 , Nieves Palma de la Peña2 , Nuria Pastor2 , Carmen Martín-Cordero1 , Eduardo Navarro3 , Felipe Cortés2 , María Jesús Ayuso1 , María Victoria Toro1
  • 1Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, Spain
  • 2Departamento de Biología Celular, Facultad de Biología, Universidad de Sevilla, Spain
  • 3Departamento de Farmacología, Facultad de Medicina, Universidad de la Laguna, Tenerife, Spain
This work has been supported by the Spanish Ministry of Science and Technology (SAF 2000-0167)
Further Information

Publication History

Received: November 22, 2002

Accepted: April 5, 2003

Publication Date:
06 October 2003 (online)

Abstract

Recent research has shown the anticancer effects of digitalis compounds suggesting their possible use in medical oncology. Four extracts obtained from the leaves of Digitalis purpurea subsp. heywoodii have been assessed for cytotoxic activity against three human cancer cell lines, using the SRB assay. All of them showed high cytotoxicity, producing IC50 values in the 0.78 - 15 μg/mL range with the methanolic extract being the most active, in non toxic concentrations. Steroid glycosides (gitoxigenin derivatives) were detected in this methanolic extract. Gitoxigenin and gitoxin were evaluated in the SRB assay using the three human cancer cell lines, showing IC50 values in the 0.13 - 2.8 μM range, with the renal adenocarcinoma cancer cell line (TK-10) being the most sensitive one. Morphological apoptosis evaluation of the methanolic extract and both compounds on the TK-10 cell line showed that their cytotoxicity was mediated by an apoptotic effect. Finally, possible mechanisms involved in apoptosis induction by digitalis compounds are discussed.

References

  • 1 Shiratori O. Growth inhibitory effect of cardiac glycosides and aglycones on neoplastic cells: in vitro and in vivo studies.  Gann. 1967;  58 521-8
  • 2 Cassady J M, Suffness M. Terpenoid antitumor targets. In: Cassady JM, Douros JD, editors Anti Cancer Agents Based on Natural Products Models. New York; Academic Press 1980: pp. 201-69
  • 3 Repke K RH, Benga G, Tager J M, editors. Biomembranes, Basic and Medical Research. Berlin; Springer Verlag 1988: pp. 161-73
  • 4 Stenkvist B, Bengtsson E, Eriksson O, Holmquist J, Nordin B, Westman-Naeser S. Cardiac glycosides and breast cancer.  Lancet. 1979;  1 563
  • 5 Stenkvist B, Bengtsson E, Eklund G. Evidence of a modifying influence of heart glucosides on the development of breast cancer.  Anal Quant Cytol. 1980;  2 49-54
  • 6 Stenkvist B, Pengtsson E, Dahlqvist B, Eriksson O, Teppo L, Idalan-Heikkila J. Cardiac glycosides and breast cancer, revisited.  N Engl J Med. 1982;  306 484
  • 7 McConey D J, Lin Y, Nutt L K, Ozel H Z, Newman R A. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells.  Cancer Res. 2000;  60 307-12
  • 8 Haux J. Digitoxin is a potential anticancer agent for several types of cancer.  Med Hypotheses:. 1999;  53 543-8
  • 9 Haux J, Klepp O, Spigset O, Tretli S. Digitoxin medication and cancer; case control and internal dose-response studies.  BMC Cancer. 2001;  1 1-6
  • 10 Monks A, Scudeiro D, Skehan P, Shoemaker R, Paull K, Vistica D. et al . Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines.  J Natl Cancer Inst. 1991;  83 757-66
  • 11 Piñero J, López-Baena M, Ortiz T, Cortés F. Apoptotic and necrotic cell death are both induced by electroporation in HL60 human promyeloid leukaemia cells.  Apoptosis. 1997;  2 214-20
  • 12 Navarro E, Alonso P J, Alonso S J, Trujillo J, Pérez C, Toro M V. et al . Cardiovascular activity of a methanolic extract of Digitalis purpurea spp. heywoodii .  J Ethnopharmacol. 2000;  71 437-42
  • 13 Haux J, Lam M, Marthinsen A BL, Strickert T, Lundgren S. Digitoxin, in non-toxic concentrations, induces apoptotic cell death in Jurkat T cell in vitro .  Z Oncol. 1999;  31 14-20
  • 14 Haux J, Solheim O, Isaksen T, Angelsen A. Digitoxin, in non-toxic concentrations, inhibits proliferation and induces cell death in prostate cancer cell lines.  Z Oncol. 2000;  32 11-6
  • 15 Sen C K, Sashwati R, Packer L. Fas mediated apoptosis of human jurkat T-cells: intracellular events and potentiation by redox-active alpha-lipoic acid.  Cell Death Differ. 1999;  6 481-91
  • 16 Abang A M. The clinical pharmacology of topoisomerase I inhibitors.  Semin Hematol. 1998;  3 13-21
  • 17 Verheye F L, Böhm L. Na+/K+-ATPase inhibitor, oubain accentuates irradiation damage in human tumour cell lines.  Radiat Oncol Invest. 1998;  6 109-19
  • 18 Malyapa R S, Wright W D, Roti J LR. Radiation sensitivity correlates with changes in DNA supercoiling and nucleoid protein content in cells of three Chinese hamster cell lines.  Radiat Res. 1999;  140 312-20
  • 19 Johnson C A, Padget K, Austin C A, Turner B M. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis.  J Biol Chem. 2001;  276 4539-42
  • 20 Cardellini E, Durban E. Phosphorylation of human topoisomerase I by protein kinase C in vitro and in phorbol 12-myristate 13-acetate-activated HL60 promyelocytic leukaemia cells.  Biochem J. 1993;  291 303-7

M. V. Toro

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Facultad de Farmacia

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