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Introduction
Colorectal cancer (CRC) is the third most common type of cancer worldwide (1). The treatment options for CRC are currently limited, with poor efficacy and marked variation in the therapeutic outcomes among patients. In the majority of cases, surgical resection remains the only curative treatment option; however, it involves costly and invasive procedures with considerable limitations. Therefore, the design of non-invasive and effective therapies is of prime importance.
Over the last decade, extensive research has focused on multiple synthetic chemotherapeutic agents that are non-invasive, but display low selectivity and severe adverse effects (2). The cornerstone of adjuvant and palliative chemotherapy for CRC is currently 5-fluorouracil (5-FU) (3). However, 5-FU has been associated with several side effects, including myelotoxicity (4), gastrointestinal disturbances (5), cardiotoxicity (6) and hepatotoxicity (7). Those limitations prompted investigators to design a more effective and safe drug, which may enhance the therapeutic benefits for CRC patients.
Epidemiological studies have consistently documented high incidence rates of CRC in Australia, New Zealand, Europe and North America. By contrast, low incidence rates of CRC have been reported in Africa and South-Central Asia, where the intake of fruits and vegetables is high (8). These epidemiological findings suggest the possibility of a causal association between habitual dietary intake and the incidence of CRC. Furthermore, these observations were substantiated by the conclusion of the World Cancer Research Fund, which reported an inverse association between the dietary intake of fruits or vegetables, flavonoid-rich diets and the incidence of CRC (9).
The basic chemical structure of flavonoids is based on a C6-C3-C6 system with a chromane ring bearing a second aromatic B ring in position 2, 3 or 4. Flavonoids are polyphenolic compounds present in a free state or as glycosides, usually O-glycosides, with the sugar moiety generally bound to the aglycone hydroxyl (OH) group at C-7 or, occasionally, C-3. The typical sugar moieties include D-glucose and L-rhamnose. Over 6,000 plant flavonoids have been described and classified into at least 10 chemical groups according to structural patterns (10). However, laboratory and epidemiological studies have focused mainly on bioflavonoids, including rutin, quercetin, chrysin, hesperetin and hesperidin, grouped under the following three flavonoid subgroups: flavonols, flavones and flavanones (Fig. 1). Flavonols, such as quercetin and its glycoside, rutin, are the most abundant...