Natural Polyphenols for Prevention and Treatment of Cancer

nutrients Review Natural Polyphenols for Prevention and Treatment of Cancer Yue Zhou 1 , Jie Zheng 1 , Ya Li 1 , Dong-Ping Xu 1 , Sha Li 2 , Yu-Ming Chen 1 and Hua-Bin Li 1,3, * 1 2 3 * Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (Y.Z.); (J.Z.); (Y.L.); (D.-P.X.); (Y.-M.C.) School of Chinese Medicine, The University of Hong Kong, Hong Kong, China; South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-sen University, Guangzhou 510006, China Correspondence: ; Tel.: +86-20-8733-2391 Received: 15 June 2016; Accepted: 12 August 2016; Published: 22 August 2016 Abstract: There is much epidemiological evidence that a diet rich in fruits and vegetables could lower the risk of certain cancers. The effect has been attributed, in part, to natural polyphenols. Besides, numerous studies have demonstrated that natural polyphenols could be used for the prevention and treatment of cancer. Potential mechanisms included antioxidant, anti-inflammation as well as the modulation of multiple molecular events involved in carcinogenesis. The current review summarized the anticancer efficacy of major polyphenol classes (flavonoids, phenolic acids, lignans and stilbenes) and discussed the potential mechanisms of action, which were based on epidemiological, in vitro, in vivo and clinical studies within the past five years. Keywords: polyphenol; flavonoid; anticancer; antioxidant; anti-inflammation 1. Introduction Globally, there were approximately 14.1 million new cancer cases in 2012, and the number was estimated to reach 25 million in 2032. Aside from the high incidence, cancer is also one of the leading causes of death. In 2012 alone, there were about 8.2 million cancer-related deaths, which were mainly attributed to lung, gastric, colorectal, liver, breast, prostate and cervical cancer [1]. The situation urges the research of cancer prevention and treatment. In the last two decades, the anticancer effects of natural polyphenols have become a hot topic in many laboratories. Meanwhile, polyphenols are potential candidates for the discovery of anticancer drugs. Polyphenols are defined as compounds having at least one aromatic ring with one or more hydroxyl functional groups attached. Natural polyphenols refer to a large group of plant secondary metabolites ranging from small molecules to highly polymerized compounds [2]. Polyphenols are widely present in foods and beverages of plant origins (e.g., fruits, vegetables, spices, soy, nuts, tea and wine) [3–5]. Based on chemical structures, natural polyphenols can be divided into five classes, including flavonoids, phenolic acids, lignans, stilbenes and other polyphenols. Flavonoids and phenolic acids are the most common classes, and account for about 60% and 30% of all natural polyphenols, respectively (Table 1) [6]. A plethora of studies have documented the anticancer effects of natural polyphenols [7–11]. Noteworthy examples include anthocyanins from blueberries, epigallocatechin gallate (EGCG) from green tea, resveratrol from red wine and isoflavones from soy. The anticancer efficacy of natural polyphenols has largely been attributed to their potent antioxidant and anti-inflammatory activities as well as their abilities to modulate molecular targets and signaling pathways, which were associated with cell survival, proliferation, differentiation, migration, angiogenesis, hormone activities, detoxification enzymes, immune responses, etc. [12,13]. Nutrients 2016, 8, 515; doi:10.3390/nu8080515 www.mdpi.com/journal/nutrients Nutrients 2016, 8, 515 2 of 35 The present review summarized recent discoveries about the anti-carcinogenic properties of natural polyphenols and discussed the mechanisms of action, which were based on evidence from epidemiological studies, laboratory experiments and clinical trials. Table 1. The classification of natural polyphenols. Classification Representative Members Major Dietary Sources anthocyanins delphinidin, pelargonidin, cyanidin, malvidin berries, grapes, cherries, plums, pomegranates flavanols epicatechin, epigallocatechin, EGCG, procyanidins apples, pears, legumes, tea, cocoa, wine flavanones hesperidin, naringenin citrus fruits flavones apigenin, chrysin, luteolin, parsley, celery, orange, onions, tea, honey, spices flavonols quercetin, kaempferol, myricetin, isorhamnetin, galangin berries, apples, broccoli, beans, tea genistein, daidzein soy hydroxybenoic acid ellagic acid, gallic acid pomegranate, grapes, berries, walnuts, chocolate, wine, green tea hydroxycinnamic acid ferulic acid, chlorogenic acid coffee, cereal grains lignans sesamin, secoisolariciresinol diglucoside flaxseeds, sesame stilbenes resveratrol, pterostilbene, piceatannol grapes, berries, red wine flavonoids isoflavonoids phenolic acids 2. Epidemiological Studies Evidence from epidemiological studies is inconsistent, especially when considering the results of prospective cohort studies (Table 2). A case-control study in Canada reported favorable effects of a high dietary intake of total flavonoids on lung cancer risks [14]. Apart from this, in a Korean study, for women, the intake of total flavonoids, as well as flavones and anthocyanidins, was inversely associated with the risk of gastric cancer [15]. However, another study in America found no significant association between flavonoids intake and the incidence or survival of gastric cancer [16]. For colorectal cancer, a meta-analysis showed protective roles of high dietary isoflavone intake [17]. Besides, a Spanish case-control study suggested that the dietary intake of total flavonoids (especially certain subclasses) and lignans might decrease colorectal cancer risks [18]. However, large prospective cohorts showed that high habitual consumption of flavonoids could not protect against colorectal cancer [19]. In addition, the Fukuoka study reported no association between total dietary polyphenols and colorectal cancer risks [20]. For hepatocellular carcinoma (HCC), the European Prospective Investigation into Cancer and Nutrition suggested that a high intake of dietary flavanols, but not total flavonoids, might modestly decrease HCC risks [21,22]. In addition, according to a meta-analysis, the risk of breast cancer was reduced in women with a high intake of flavonols and flavones [23]. Studies also suggested that soy isoflavone intake reduced breast cancer risk for Asian women, which was more potent for post-menopausal women (OR 0.46, 95% CI 0.28–0.78) than for premenopausal women (OR 0.63, 95% CI 0.50–0.80). However, for women in Western countries, no significant association could be found, which might due to low levels of isoflavone consumption in the Western population [24,25]. In addition, the estrogen receptor (ER) status might modify the association. For example, a U.S. prospective cohort study showe (...truncated)