Cytotoxicity and DNA binding characteristics of dextran-conjugated doxorubicins

Mengsu Yang*, Hing Leung Chan, Wing Lam, David W F FONG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The antitumor antibiotic doxorubicin was conjugated with polymeric dextrans of various molecular weights and the cytotoxicity of the conjugates against human carcinoma KB-3-1 cells and its multidrug-resistant subclone KB- V-1 cells was measured by tetrazolium salt MTT assay. The conjugates were much less toxic to the KB-3-1 cells than the free doxorubicin but exhibited similar toxicity to the KB-V-1 cells. The conjugate-DNA interactions were monitored in real-time using an optical biosensor based on evanescent wave detection to obtain the association (k(a)) and dissociation (k(d)) rate constants as well as the equilibrium binding constants (K(A)) of the bindings. Both k(a) and k(d) values for the conjugates are more than three magnitudes smaller than those for free doxorubicin, while the K(A) values of the conjugate-DNA complexes are only about 10 times smaller than that of the free doxorubicin-DNA complex. The results indicate that the cytotoxicity and the DNA-binding kinetics of doxorubicin may be modified with dextran conjugation. The K(A) values obtained from the biosensor measurements were in close agreement with those determined in solution by fluorescent titration method, verifying the utility of the label-free biosensing measurements as an efficient method for studying ligand-DNA interactions.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1380
Issue number3
DOIs
Publication statusPublished - 8 May 1998

Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

User-Defined Keywords

  • Doxorubicin conjugate
  • Ligand-DNA interaction
  • Optical biosensor

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