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The environment of phytonutrients may contribute to their bioefficacy against cancer

The reductionist approach contributes greatly to our understanding of anticancer properties of phytonutrients, but in vitro studies demand concentrations that are 100–1000 times higher than achievable in humans, producing results with little physiologic relevance, resulting in disappointing outcomes in clinical trials. However, maintaining these bioactives in the presence of other compounds originally derived from the food/extract of origin may synergistically lower the bioactive dose so translatability becomes feasible. The objective of this study was to determine if bioefficacy of phytonutrients can be enhanced when used in combination at doses that are ineffective when used in isolation. Proliferation of CWR22Rv1 PCa cells was evaluated and synergy was assessed when treated with turmeric, Chinese goldthread and their bioactives (curcumin and ar‐turmerone, berberine and coptisine) in isolation or in combination. Combining bioactives or herbal extracts were highly synergistic at physiologic concentrations where the dose reduction index was up to 190 fold. Berberine and curcumin (in isolation) were not as potent as their extracts of origin. Combinations of herbal extracts and/or their isolated bioactives lowered concentrations that approached physiologic relevance and may account for why foods/plant extracts are more likely to be beneficial against cancer compared with isolated components.