The efficacy of anticancer DNA alkylating agents depends on the activity of drug metabolizing enzymes, and reductases may be a particularly important yet under-addressed group of enzymes. NADPH-dependent reductases, such as prostaglandin reductase (PTGRs) and thioredoxin reductase (TrxR), are both susceptible to modulation by bioactive food components and influence the toxicity of the reductase-activated drug acylfulvene. In this study, we combined targeted (SRM) and untargeted (SILAC) proteomic strategies to evaluate cellular reductase responses to sodium selenite, sulforaphane or dithiolethione. Quantitative enzyme levels were correlated with metabolic capacities as assessed by spectroscopic assays with activity probes. With these assays, we established a new and quantitative experimental approach for testing possible food-drug interactions. Relationships between enzyme capacities, changes in enzyme levels, and drug efficacy will be discussed.

Mapping reductase enzyme modulation in human colorectal cancer cells

244th National Meeting (2012)

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