Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy

Abstract

Natural polyphenols are organic chemicals which contain phenol units in their structures. They show antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Still, definitively demonstrating the human benefits of isolated polyphenolic compounds (alone or in combination) using modern scientific methodology has proved challenging. The most common discrepancy between experimental and clinical observations is the use of nonphysiologically relevant concentrations of polyphenols in mechanistic studies. Thus, it remains highly controversial how applicable underlying mechanisms are with bioavailable concentrations and biological half-life. The present Perspective analyses proposed antitumor mechanisms, in vivo reported antitumor effects, and possible mechanisms that may explain discrepancies between bioavailability and bioefficacy. Polyphenol metabolism and possible toxic side effects are also considered. Our main conclusion emphasizes that these natural molecules (and their chemical derivatives) indeed can be very useful, not only as cancer chemopreventive agents but also in oncotherapy.

The red wine component ellagic acid induces autophagy and exhibits anti‐lung cancer activity in vitro and in vivo

“…Polyphenols are believed to mediate many of the health benefits of moderate wine consumption. Some of these polyphenols have inhibitory effects and chemoprevention potentials in several types of cancers . Here, we examined the potential anti‐lung cancer effects of 11 red wine polyphenols and found that EA exhibited almost the same effect as resveratrol in lung cancer (Figure ).…”

Oxidative stress and antioxidants in the pathophysiology of malignant melanoma

“…One class of antioxidant compounds that have been studied extensively as anticancer agents are the polyphenols. An abundance of evidence has demonstrated polyphenols have anticancer activity in vitro and in animal models (Estrela et al, 2017). Adverse effects of polyphenols have also been reported.…”

“…This represents a potential paradigm shift in how antioxidant-based cancer treatments are developed. Moreover, it is also essential to keep in mind that combination of two or more polyphenols (at non-toxic and pharmacologically acceptable doses in humans) may show synergic/additive effects (Estrela et al, 2017).…”

Palladium‐catalyzed decarboxylative coupling of α,β‐unsaturated carboxylic acids with aryl tosylates

“…[17][18][19][20] Traditional syntheses of this substructure, such as Wittig or Julia olefinations, [21,22] Pd-catalyzed Heck-type coupling [23][24][25][26][27] and some reduction and condensation methods using suitable substrates, [28][29][30] are waste-intensive, limited in scope and/or require multistep syntheses of starting materials. (E)-1,2-Diarylethene scaffolds have received a great deal of attention from biology and synthetic chemistry researchers in the past decade because of their wide-ranging spectrum of biological activities and broad applications in various fields of research.…”

“…In addition, (E)-1,2-diarylethenes are also considered as important building blocks in synthetic dyes and molecules used in organic light-emitting diodes and liquid crystals. [17][18][19][20] Traditional syntheses of this substructure, such as Wittig or Julia olefinations, [21,22] Pd-catalyzed Heck-type coupling [23][24][25][26][27] and some reduction and condensation methods using suitable substrates, [28][29][30] are waste-intensive, limited in scope and/or require multistep syntheses of starting materials.…”