A daidzein-daunomycin conjugate improves the therapeutic response in an animal model of ovarian carcinoma

Dalia Somjen, Sara Katzburg, Nava Nevo, Batya Gayer, Richard P. Hodge, Misty D. Renevey, Vyacheslav Kalchenko, Asher Meshorer, Naftali Stern, Fortune Kohen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The use of daunomycin against neoplasms is limited due to its severe cardiotoxicity. The cytotoxicity of daunomycin can be minimized by linking it to an affinity tag. Since ovarian cancer cells are sensitive to isoflavone action, we synthesized a daidzein daunomycin conjugate. In MLS human ovarian cancer cells, the conjugate was shown to have a larger cytotoxic effect than daunomycin per se at a low concentration. The conjugate was then tested in vivo in mice carrying MLS xenografts. Tumour growth in the groups of conjugate and daunomycin was inhibited by >50% as compared to vehicle treated mice. In contrast to daunomycin treated mice, no weight reduction or death was seen in mice treated with the conjugate. In vivo imaging of the fluorescence signal generated by daunomycin indicated uptake of both conjugate and daunomycin by the tumour. Tumour fluorescence was, however, higher in the conjugate treated mice than in the daunomycin treated mice, thus suggesting specific delivery of the drug to the tumour. Histological examination of myocardial tissue indicated that only the daunomycin, but not conjugate treated mice showed cardiac damage. These results indicate that targeting of daunomycin via carboxymethyldaidzein retains daunomycin's cytotoxic effects while averting its toxicity in an ovarian xenograft.

Original languageEnglish (US)
Pages (from-to)144-149
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume110
Issue number1-2
DOIs
StatePublished - May 1 2008

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Keywords

  • Daidzein
  • Daunomycin
  • Isoflavone
  • Ovarian carcinoma
  • Site directed chemotherapy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Somjen, D., Katzburg, S., Nevo, N., Gayer, B., Hodge, R. P., Renevey, M. D., Kalchenko, V., Meshorer, A., Stern, N., & Kohen, F. (2008). A daidzein-daunomycin conjugate improves the therapeutic response in an animal model of ovarian carcinoma. Journal of Steroid Biochemistry and Molecular Biology, 110(1-2), 144-149. https://doi.org/10.1016/j.jsbmb.2008.03.033