Cancer prevention ICancer Prevention With Natural Compounds
Section snippets
Green Tea
Next to water, tea is the most popular beverage consumed in the world and is distinguished by the presence of a group of polyphenols called catechins. A growing body of evidence from laboratory animal studies demonstrates that tea consumption has an inhibitory effect on carcinogenesis at various organ sites. For example, oral administration of tea infusion can inhibit the development of experimental rodent skin tumors,36 growth of implanted tumor cells,37 invasion and metastasis of malignant
Curcumin
The Zingiberaceae is a well-known plant family in Southeast Asia, and numerous species are being used in traditional medicine for the treatment of several diseases. The representative chemopreventive agent is curcumin. This compound has been shown to exert anti-carcinogenic effects in a diverse array of animal and cell culture models. Surh and Chun have summarized mechanistic and anti-carcinogenesis studies conducted with curcumin.90 Inhibition of tumor promotion is predominant. Curcumin (
Resveratrol and Piceatannol
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) (Figure 1, Figure 2, Figure 3C), a naturally occurring polyhydroxylated stilbene, is widely present in grapes, red wine, mulberries, and other edible plants. This naturally occurring stilbene exerts protective effects against experimentally induced carcinogenesis.110, 111, 112, 113, 114 However, the molecular mechanisms underlying chemopreventive activity of resveratrol remain largely unresolved. Besides its well-defined antioxidant potential,
Lycopene
Lycopene (Figure 3D) is a carotenoid that gives tomato its red color. It is also found in guava, watermelon, and pink grapefruit, but it is most abundant in red tomatoes and processed tomato products, especially tomato paste. Because of its potent antioxidant effect, lycopene has drawn much attention as a cancer preventive agent. Population studies have shown that high intake of lycopene is inversely associated with the incidence of certain types of cancers, including those of the digestive
Pomegranate
The fruit of the tree Punica granatum (Figure 1), grown mainly in the Mediterranean region, has been shown to possess many medicinal properties such as being anti-oxidant and anti-inflammatory.155 The anti-oxidant activity of flavonoids obtained from pomegranate juice was observed to be close to that of butylated hydroxyanisole and green tea and significantly greater than red wine.156, 157, 158 The polyphenol-rich fractions of pomegranate inhibited growth of breast cancer cells159 and decreased
Luteolin
Luteolin (Figure 3E) is a flavonoid found in a variety of vegetables, especially in broccoli, celery, cabbage, spinach, green pepper, and cauliflower. It has anti-inflammatory and anti-cancer effects.168 Luteolin has been found to induce cell cycle arrest and apoptosis in a variety of cancer cells including oral squamous cancer,169 esophageal cancer,170 lung cancer,171 colon cancer,172 and hepatoma.173 Luteolin inhibited cell growth and induced apoptosis in prostate cancer cells both in vitro
Soy Isoflavones
Soy isoflavones include genistein, daidzein, and glycitein. Genistein is the most active and abundant isoflavone (Figures 2 and 3F) found in soybeans (Figure 1) and soy products. It has selective estrogen receptor modulator (SERM) properties similar to tamoxifen and raloxifene.178 Epidemiological studies show an inverse association between dietary soy consumption and the risk of prostate,179 breast,180, 181 and endometrial182 cancers. Dietary genistein supplementation decreased the development
Omega-3 Fatty Acids
The benefits of omega-3 fatty acids have been cited for a variety of medical conditions,204, 205 including cancer prevention and cancer-induced cachexia.206 The ability of omega-3 fatty acids (eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA]) to reduce inflammatory cytokines has generated much interest in the possibility of their modifying the acute phase response in cachectic patients—specifically to decrease the production of acute-phase proteins. Fish oil supplements rich in
Thymoquinone
The anti-tumor activity of thymoquinone (TQ) seems promising both for chemoprevention and preventing drug-induced toxicity. Additionally, this compound exhibits some selectivity to cancer cells, since normal human pancreatic ductal epithelial cells (HPDEs) and mouse keratinocytes are resistant to the apoptotic effects of.213, 214 TQ also has been shown to have anti-inflammatory activities in pancreatic ductal adenocarcinoma (PDA) cells, and these activities are paralleled by inhibition of NF-κB.
Other Natural Agents
There are many other dietary and medicinal botanicals and other natural compounds that are currently under investigation for their potential cancer chemopreventive effects. These include ellagic acid, some triterpenes (such as lupeol, betulinic acid, ginsenosides, oleanolic acid, etc), and ginkolide B. Ellagic acid (Figure 3I) is an antioxidant polyphenol present in many fruits and vegetables including grapes, strawberries, raspberries, pomegranate, and nuts, which exhibited chemopreventive
Mechanisms of Natural Chemopreventive Compounds
Recent entire genomic sequencing results revealed that a lung tumor carried more than 23,000 mutations. A smoker develops one mutation for every 15 cigarettes smoked. This indicates the complexity of human cancers. Furthermore, there are approximately 25,431 human genes, and out of these 2,995 genes have been linked with 153 cell signaling pathways and about 350 genes have been linked directly with any given cancer. Thus, targeting a single gene is unlikely to treat or prevent any cancer. There
Conclusions
The results of epidemiological, preclinical, and early clinical studies suggest that selected dietary products may play a role in cancer prevention and treatment. Many of these agents target multiple signal transduction pathways. The key challenge to researchers is how best to use this information for effective cancer prevention and treatment. Development of synthetic analogues of natural compounds and/or using nanotechnology approach may increase the potency and bioavailability of these
Acknowledgment
D.M.S., F.R.K., and O.K. are Distinguished Cancer Scholars of the Georgia Cancer Coalition (GCC).
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