Bioreduction-Mediated Food-Drug Interactions: Opportunities for Oncology Nutrition

Abstract

Chemical and biochemical processes underlying food-drug interactions in cancer therapy have not been well addressed with a systematic focus, even though they offer significant potential for enhancing the efficacy of cancer chemotherapy. Bioreductive anticancer drugs are metabolically activated by reductase enzymes. The levels and activities of relevant metabolic enzymes are regulated by transcription factors, which are under the control of chemical interactions with small molecules, including bioactive food components (BFCs) such as minerals, vitamins, and a variety of phytochemicals. One important and well-established process is the upregulation of enzymes involved in xenobiotic metabolism and redox regulation. Thus, BFCs might help to overcome resistances of some cancer cells towards anticancer agents or to increase efficacy by sensitizing cancer cells towards synergistic drugs. By understanding chemical and biochemical processes involved in food-drug interactions, not only can the risk of harmful food-drug interactions be diminished, but appropriate nutritional recommendations for cancer patients can be made and new functional foods with specific benefits in anticancer therapy may be developed.

Induction of Complementary Function Reductase Enzymes in Colon Cancer Cells by Dithiole‐3‐thione versus Sodium Selenite

“…The potential for pharmacological induction of reductase enzymes suggests opportunities for combination therapies or chemoprevention , but there are knowledge gaps regarding quantitative relationships between biotransformation efficiency and how particular proteins give rise to a phenotype attributable to bioactive agents. Modern quantitative proteomics‐oriented strategies allow one to quantify specific proteins in complex biological fluids .…”

Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation

“…Selectively preconditioning cancer cells with non-toxic amounts of a natural bioactive compound may safely enhance drug susceptibility. These compounds often activate drugs by upregulating the activity of drug metabolic enzymes; thus, they may significantly affect treatment outcomes despite low exposure (45)(46)(47).…”

Sulforaphane Preconditioning Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A

“…Cancer drugs are often associated with severe side effects that limit dosing potential, therefore prodrugs that require bioactivation in target cells are actively pursued as a strategy to promote therapeutic selectivity [ 1 ]. To further differentiate between target and non-target cells, particularly for enzyme-activated prodrugs, a novel alternative approach is to selectively precondition cancer cells with non-toxic amounts of a natural bioactive compound to safely enhance drug susceptibility [ 2 ]. These compounds often up-regulate drug metabolizing enzymes that bioactivate drugs, therefore despite low exposures, they may significantly impact therapy outcomes [ 3 ].…”