**3. Conclusion**

Although there is a lack of definitive evidence for the association of Mediterranean diet with various types of cancer and whatever the final assessment of the overall contribution of such diets to cancer prevention turns out to be, there is no doubt that the phytochemicals they contain do exert a range of fascinating and potentially important biological effects on human health. Over the last decade, a broad spectrum of plant natural compounds, that have gained much attention for consideration as cancer chemopreventive or therapeutic agents, has been isolated from traditional herbal medicines, spices, fruits, and vegetables. These plant secondary metabolites as medicines, dietary supplements or "health food" ingredients may exhibit considerable benefits over synthetic drug approaches, as they offer an inexpensive, convenient, readily applicable and accessible health-care approach for prevention, control and management of diseases such as cancer. The continued emergence of new evidence for the multifunctional effects of these products has certainly provided much impetus for future research into their modes of action and their application in cancer prevention and treatment. Advances in cellular, biochemical and molecular biology techniques and experimental approaches using transcriptome, proteome, metabolome and bioinformatics analyses have provided useful new insights into cancer therapeutics.

One obvious weakness of the current state of research, is that much of it has been conducted in vitro, with little regard for the bioavailability of the compounds studied. In most cases the small proportion of any compound that is absorbed undergoes extensive metabolism before reaching target organs, and the products are readily excreted. In the future, long-term systematic intervention trials, that will take into consideration the bioavailability and metabolism of those phytochemicals, will be essential to gather good evidence of their anticancer potential. Such strategies will contribute to a full risk–benefit analysis, based on a thorough understanding of their overall biological effects. With the expected advances in our understanding of the specific signaling pathways, transcription factors and molecular target genes affected by chemopreventive plant compounds, these natural products will offer a great promise as anticancer therapeutics or chemopreventive agents. Moreover, further development of these potent natural products will improve the efficacy of targeted therapeutic strategies to win the long run battle against cancer.

#### **4. References**

276 Cancer Prevention – From Mechanisms to Translational Benefits

Historical and current studies and surveys indicate, that the region of the Mediterranean has been distinguished throughout generations with a rich inventory of natural medicinal herbs. By expanding upon the wisdom of the Greeks over the centuries, indigenous medicine has contributed greatly to the development of modern medicine in Europe and remains one of the closest forms of original European medicine. A diet in which culinary herbs are used generously to flavor food, provides a variety of active phytochemicals that promote health and protect against chronic diseases such as cancer. Charlemagne was correct when he said "a herb is a friend of physicians and the praise of cooks". Nevertheless, whereas some herbal products may be safe and may contain active constituents that have beneficial physiologic effects, others may be unsafe to use. The Food and Drug Administration has classified several herbs as unsafe, even in small amounts, and hence they should not be used in either foods or beverages (Craig, 1999). Some herbs are safe in modest amounts but they may become toxic at higher doses. Overall, when herbs are prescribed appropriately, the safety of traditional herbal medications is high. Any plant parts used or prescribed by ethnopharmacologists should be tested for safety before being recommended for human

Although there is a lack of definitive evidence for the association of Mediterranean diet with various types of cancer and whatever the final assessment of the overall contribution of such diets to cancer prevention turns out to be, there is no doubt that the phytochemicals they contain do exert a range of fascinating and potentially important biological effects on human health. Over the last decade, a broad spectrum of plant natural compounds, that have gained much attention for consideration as cancer chemopreventive or therapeutic agents, has been isolated from traditional herbal medicines, spices, fruits, and vegetables. These plant secondary metabolites as medicines, dietary supplements or "health food" ingredients may exhibit considerable benefits over synthetic drug approaches, as they offer an inexpensive, convenient, readily applicable and accessible health-care approach for prevention, control and management of diseases such as cancer. The continued emergence of new evidence for the multifunctional effects of these products has certainly provided much impetus for future research into their modes of action and their application in cancer prevention and treatment. Advances in cellular, biochemical and molecular biology techniques and experimental approaches using transcriptome, proteome, metabolome and

bioinformatics analyses have provided useful new insights into cancer therapeutics.

One obvious weakness of the current state of research, is that much of it has been conducted in vitro, with little regard for the bioavailability of the compounds studied. In most cases the small proportion of any compound that is absorbed undergoes extensive metabolism before reaching target organs, and the products are readily excreted. In the future, long-term systematic intervention trials, that will take into consideration the bioavailability and metabolism of those phytochemicals, will be essential to gather good evidence of their anticancer potential. Such strategies will contribute to a full risk–benefit analysis, based on a thorough understanding of their overall biological effects. With the expected advances in our understanding of the specific signaling pathways, transcription factors and molecular target genes affected by chemopreventive plant compounds, these natural products will offer a great promise as anticancer therapeutics or chemopreventive agents. Moreover,

use.

**3. Conclusion** 


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**11** 

*Australia* 

**in Prostate Cancer** 

Qihan Dong4,5 and Paul L de Souza1\*

*Liverpool Hospital, Campbelltown and Liverpool, NSW 2St. George Hospital Clinical School, UNSW, Kogarah, NSW* 

*5University of Sydney Central Clinical School, Sydney, NSW* 

**Dietary Manipulation for Therapeutic Effect** 

Carol A Gano1, Kieran Scott2, Joseph Bucci2, Heather Greenfield3,

*3Adjunct Professor, University of Sydney and University of NSW, Randwick, NSW 4University of Western Sydney School of Health Science, Campbelltown, NSW* 

Given that there is a wealth of literature on the potential effect of a wide variety of phytochemicals on the growth of prostate cancer cells, we have limited our discussion to arguably four of the most important: isoflavones, lycopene, resveratrol, and curcumin. The focus of this review is on the clinical pharmacology of these compounds, as there are already an extensive number of reviews in the literature on all of these compounds for various cancers, including our previous review of isoflavones in prostate cancer (de Souza et al., 2009). Here, we use the loose term "phytochemicals" to describe this group of plant– based compounds with biological activity *in vitro,* for simplicity. Like other phytochemicals, isoflavones, lycopene, resveratrol and curcumin have a wide variety of potential mechanisms of action in many different cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, but in this

Reactive oxidative species (ROS) may have an overall contribution to the development of cancer (Kryston et al., 2011; Benhar et al., 2002), but the mechanism is far from clear, though the general thrust of the argument is that DNA damage wrought by ROS may be left unchecked or uncorrected by mismatch repair enzymes, thereby contributing to carcinogenesis (Benhar et al., 2002, Ziech et al., 2010, Kryston et al., 2011). However, it is also apparent that higher levels of ROS can activate intrinsic apoptosis (Benhar et al., 2002), which would imply that antioxidants should not be used indiscriminately as it could prevent a desirable outcome in cancer cells. The biological mechanisms underpinning some of the potential anti-oxidant mechanisms of phytochemicals are complex and as yet speculative, and will not be discussed here. Instead, readers are referred to recent reviews

review, we will be focusing on studies specifically in prostate cancer.

(Ziech et al., 2010; Kryston et al., 2011).

Corresponding author

 \*

**1. Introduction** 

*1University of Western Sydney School of Medicine and Ingham Institute,* 

