Mechanism of action and spectrum of cell lines sensitive to a doxorubicin-transferrin conjugate

Cancer Chemotherapy and Pharmacology
B T LaiK W Lanks

Abstract

A transferrin-doxorubicin conjugate exhibited greatly increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cultured tumor cell lines. An L929 cell line selected for doxorubicin resistance was as sensitive to the transferrin-doxorubicin conjugate as was the parental unselected line. Quantitative measurements of doxorubicin fluorescence in single L929 cells showed that uptake was similar in amount when cells were exposed to equivalent concentrations of doxorubicin presented either free or as the transferrin-doxorubicin conjugate. However, unconjugated drug fluorescence was distributed in membranes, cytoplasm and nucleus, whereas conjugate fluorescence was confined mainly to the cytoplasmic compartment. In as much as NADPH-dependent free radical formation is a known mechanism of doxorubicin cytotoxicity, localization in the vicinity of NADPH production might facilitate this cytotoxic pathway. Neither cytotoxicity nor uptake of the conjugate quantified by doxorubicin fluorescence was significantly blocked by excess free transferrin, and the conjugate was not concentrated in the plasma membrane at 4 degrees C. These findings suggest that conjugate internalization is not entirely dependent on transferrin re...Continue Reading

Citations

Mar 6, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kun NaYou Han Bae
Apr 5, 2002·Medicinal Research Reviews·Hongyan Li, Zhong Ming Qian
Apr 28, 2010·ACS Applied Materials & Interfaces·Jia-Hui LiuYa-Ping Sun
Dec 12, 2020·Cancer Treatment and Research Communications·Sanjay KumarShefali Shukla
Aug 22, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Tracy R DanielsManuel L Penichet
Aug 20, 2011·Biochimica Et Biophysica Acta·Tracy R DanielsManuel L Penichet

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