Green Cancer Prevention and Beyond

Abstract

The concept of green chemoprevention was introduced in 2012 by Drs. Jed Fahey and Thomas Kensler as whole-plant foods and/or extract-based interventions demonstrating cancer prevention activity. Refining concepts and research demonstrating proof-of-principle approaches are highlighted within this review. Early approaches included extensively investigated whole foods, including broccoli sprouts and black raspberries showing dose-responsive effects across a range of activities in both animals and humans with minimal or no apparent toxicity. A recent randomized crossover trial evaluating the detoxification of tobacco carcinogens by a broccoli seed and sprout extract in the high-risk cohort of current smokers highlights the use of a dietary supplement as a potential next-generation green chemoprevention or green cancer prevention approach. Challenges are addressed, including the selection of dose, duration and mode of delivery, choice of control group, and standardization of the plant food or extract. Identification and characterization of molecular targets and careful selection of high-risk cohorts for study are additional important considerations when designing studies. Goals for precision green cancer prevention include acquiring robust evidence from carefully controlled human studies linking plant foods, extracts, and compounds to modulation of targets for cancer risk reduction in individual cancer types.

Figure 1.

Bioprocessing of select green cancer prevention food components. Created with BioRender.com. Legend, Human bioprocessing of select bioactive components in green cancer prevention. Ingestion, Food mastication reduces berries and broccoli sprouts to smaller food particles. Mastication of broccoli sprout cell walls releases its myrosinase catalyzing glucosinolate hydrolysis for sulforaphane release. Digestion, Masticated berry food particles release small amounts of free ellagic acid for limited gastric absorption. More complex berry ellagitannins are also released and undergo further digestion to ellagic acid. Masticated broccoli sprouts food particles enter the gastric compartment for continued sulforaphane processing and release. Gastric enzymes mix with both berry and broccoli sprout food particles forming chyme entering the small intestine. Absorption, Digested berry-derived food particles undergo limited absorption in the small intestine and move into the large intestine for further microbial bioprocessing. Sulforaphane, a major broccoli sprout glucosinolate, is primarily absorbed in the small intestine entering hepatic circulation for systemic distribution. Transformation, Berry-derived ellagic acid enters the large colon where resident microbiota metabolizes ellagic acid to urolithins for colonocyte absorption and transport into the systemic circulation. Little, if any, sulforaphane enters the colonic lumen as it was largely absorbed in the small intestine.