Cancer preventive effects of flavonoids—a review

Abstract

A cancer protective effect from plant-derived foods has been found with uncommon consistency in epidemiologic studies. However, it has been difficult to identify specific components responsible for this effect. Many phytochemicals have been shown to be biologically active and they may interact to protect against cancer. In recent years, experimental studies have provided growing evidence for the beneficial action of flavonoids on multiple cancer-related biological pathways (carcinogen bioactivation, cell-signaling, cell cycle regulation, angiogenesis, oxidative stress, inflammation). Although the epidemiologic data on flavonoids and cancer are still limited and conflicting, some protective associations have been suggested for flavonoid-rich foods (soy and premenopausal breast cancer; green tea and stomach cancer; onion and lung cancer). This review focuses on the biological effects of the main flavonoids, as well as the epidemiologic evidence that support their potential cancer protective properties.

Introduction

The scientific evidence that plant-based diets, in particular those rich in vegetables and fruits, protect against cancers of various sites has been found to be strong and consistent by a recent expert panel 〚1〛. This effect may result from the low energy content of these diets and/or from their specific constituents. Although plant-derived foods vary in their nutritional composition profiles, they generally are good sources of important nutrients (i.e., fiber, carotenoids, vitamin C, folate, minerals) and of many less well-characterized bioactive compounds (phytochemicals). Accordingly, public health authorities have uniformly emphasized the potential benefits of fruits and vegetables in their recommendations to the public. Moreover, the identification of the specific constituents of these foods that are protective may lead to additional means of prevention, such as the fortification of the food supply (e.g., folate), the use of chemopreventive agents in high risk individuals and the engineering of “designer foods” enriched in protective compounds.

However, the identification of the protective constituents in plant-derived foods can be problematic, as illustrated by the chemoprevention research conducted with beta-carotene. This pro-vitamin A carotenoid has been found to be inversely associated with cancer risk in epidemiologic studies and showed promising results in laboratory studies 〚2〛. Early on, this nutrient was singled out for randomized chemoprevention trials among individuals at high risk (smokers, asbestos-exposed workers) or low risk (US physicians) for lung cancer 〚3〛, 〚4〛, 〚5〛. The results of these large beta-carotene trials have been disappointing as they showed no beneficial effect, and even, in high risk individuals, a detrimental effect, on lung cancer incidence 〚3〛, 〚4〛, 〚5〛. However, it has been apparent for some time, that the association with beta-carotene is difficult to distinguish from that of vegetables in observational dietary studies and that, indeed, similar associations can be demonstrated between cancer and other phytochemicals. For example, in a case-control study in Hawaii, we found inverse associations of lung cancer with total intakes of vegetables and subgroups of vegetables particularly rich in other phytochemicals (dark green vegetables, cruciferous vegetables, tomatoes, carrots) that were stronger than that with beta-carotene 〚6〛. We also found independent associations of similar magnitude with other carotenoids (lutein, alpha-carotene) 〚7〛. These various active components may interact additively or synergistically to protect against cancer. Thus, it may be more productive to study the preventive effect of entire foods than that of single nutrients which may, especially at non-physiological dose, have different properties than when given as part of food matrix in a regular diet. Indeed, recent experimental studies have shown that, in some circumstances, beta-carotene may act as a pro-oxidant 〚8〛.