Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: Phenolic acids, monophenol, polyphenol, and their derivatives

Abstract

Cancer metastasis is the major cause of cancer-related death, and chemoprevention is defined as the use of natural or synthetic substances to prevent cancer formation or cancer progress. Evidence that phenolic compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. Curcumin, resveratrol, and their related derivatives are the most studied compounds in this topic so far; gallic acid, chlorogenic acid, caffeic acid, carnosol, capsaicin, 6-shogaol, 6-gingerol, and their corresponding derivatives are also suggested to be the active members of the phenolic family on anti-invasion and anti-metastasis. Because metastasis occurs through a multistep process, these bioactives might act on a variety of stages of the metastatic process to prevent tumor cells from metastasizing. This review summarizes the common protein targets and signaling pathways for the inhibition of invasion and metastasis as well as past publications on the in vitro and in vivo effects and molecular mechanisms of phenolic acids, monophenol, polyphenol, and their derivatives, except flavonoids, on cancer invasion and metastasis. Based on these data, we conclude that the daily consumption of natural dietary components that are rich in phenolics could be beneficial for the prevention of cancer metastasis.

Introduction

Cancer metastasis is the spread of cancer cells from the primary neoplasm to distant sites where secondary tumors are formed. Metastasis occurs through a complex multistep process beginning with the entrance of cells from the primary tumor into the vasculature, migration to distant organs, adhesion to endothelial cells lining the blood vessels, and extravasation leading to infiltration into the underlying tissue. Metastasis causes the largest challenge in cancer treatment and is the major cause of cancer-related death.¹ Following the diagnosis of cancer, additional chemotherapy may be recommended to prevent a local recurrence of the primary tumor and the spread of tumor cells. However, severe side effects may occur at the effective dose of many chemotherapeutics. Therefore, in addition to minimizing the growth of existing tumors, treatments that limit its spread to new sites and block invasion are valid strategies to enhance the survival of cancer patients.2, 3

Phenolic compounds originate from one of the main classes of secondary metabolites in plants, are natural phytochemicals derived mostly from phenylalanine and less often from tyrosine, and are widely present in food and nutraceuticals.4, 5, 6 Chemically, phenolic compounds are diverse in structure but can be defined as substances possessing at least one aromatic ring bearing one or more hydroxyl groups. According to the number of hydroxylated aromatic rings and the type of functional moiety, phenolic compounds can be simply categorized as phenolic acids, polyphenols, or monophenols. However, a large variety of phenolic derivatives including simple phenols, phenylpropanoids, benzoic acid derivatives, flavonoids, and stilbene were also found in plants and foods. Additionally, many phenolic compounds are polymerized into larger molecules such as condensed tannins (e.g., proanthocyanidins), lignans, and lignins. At first, phenolic compounds attracted much attention because of their strong antioxidant activity. Shortly afterward, potentially protective effects against oxidative damage diseases (e.g., coronary heart disease, stroke, and cancers) of phenolics in natural food were found. Recently, evidence suggesting phenolic compounds possess an effective inhibitory effect on cancer invasion and metastasis is also increasingly being reported in the scientific literature.

Chemoprevention is defined as the use of natural or synthetic substances to prevent cancer formation or cancer progression. Studies have shown that natural phytochemicals containing phenolic compounds derived from certain plants have the capability to prevent cancer metastasis.⁷ Phenolic compounds are comprised of a large aggregation of phytochemicals that consist of numerous subgroups defined by their structural characteristics. The literature describing the bioactivity of all phenolic compounds is too vast to summarize in a single article. This review therefore focuses on the in vitro and in vivo data on the anti-invasive and anti-metastatic effects and underlying molecular signaling mechanisms of phenolic acids, monophenol, polyphenol, and their derivatives. The flavonoids, a very large subgroup of phenolics, will therefore not be addressed here.