A switching mechanism in doxorubicin bioactivation can be exploited to control doxorubicin toxicity.

ABSTRACT: Although doxorubicin toxicity in cancer cells is multifactorial, the enzymatic bioactivation of the drug can significantly contribute to its cytotoxicity. Previous research has identified most of the components that comprise the doxorubicin bioactivation network; however, adaptation of the network to changes in doxorubicin treatment or to patient-specific changes in network components is much less understood. To investigate the properties of the coupled reduction/oxidation reactions of the doxorubicin bioactivation network, we analyzed metabolic differences between two patient-derived acute lymphoblastic leukemia (ALL) cell lines exhibiting varied doxorubicin sensitivities. We developed computational models that accurately predicted doxorubicin bioactivation in both ALL cell lines at high

SUBMITTER: Finn NA 

PROVIDER: S-EPMC3174179 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature