PMID: 9555082May 23, 1998Paper

Cytotoxicity and DNA binding characteristics of dextran-conjugated doxorubicins

Biochimica Et Biophysica Acta
M YangW F Fong

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 (ka) and dissociation (kd) rate constants as well as the equilibrium binding constants (KA) of the bindings. Both ka and kd values for the conjugates are more than three magnitudes smaller than those for free doxorubicin, while the KA 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 KA 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 ...Continue Reading

References

Jan 1, 1978·Methods in Enzymology·F W Dahlquist
Jan 1, 1991·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J CummingsJ F Smyth
Jan 1, 1989·Annual Review of Biochemistry·J A Endicott, V Ling
Sep 19, 1989·Biochimica Et Biophysica Acta·J TarasiukL Gattegno
Dec 1, 1987·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M C WillinghamI H Pastan
Oct 29, 1986·Biochimica Et Biophysica Acta·F BarceloJ M Gonzalez-Ros
Mar 1, 1985·Somatic Cell and Molecular Genetics·S AkiyamaM M Gottesman
Aug 17, 1982·Biochemistry·J B ChairesD M Crothers
Oct 10, 1995·Analytical Biochemistry·P R EdwardsR J Leatherbarrow
Oct 9, 1996·Biochimica Et Biophysica Acta·I Bosch, J Croop

❮ Previous
Next ❯

Citations

Sep 16, 2000·Journal of Biochemical and Biophysical Methods·B C WeimerX Wang
Oct 6, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·R Mehvar
Dec 28, 1999·Journal of Molecular Recognition : JMR·D G Myszka

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.