Broccoli, PTEN deletion and prostate cancer: where is the link ?

The concept that vegetables and fruits are relevant sources of cancer-preventive substances is strongly supported by population studies.

Among others, cruciferous vegetables like broccoli, cabbage, cauliflower and brussels sprouts are thought to affect the development of various types of cancers and especially prostate tumors.

Yet, the identification of the molecular mechanisms by which the ‘active’ compounds contained in these vegetables mediate their anticancer activity has historically lagged behind. Accordingly, direct laboratory evidence of how individual nutrients affect cancer genes and the pathways they control remains the major obstacle to progress in this research field.

Here we review a recent report investigating the interaction between sulforaphane, a dietary isothiocyanate derived from broccoli, and expression of the PTEN tumor suppressor gene in pre malignant prostate tissue.

Introduction

The rationale for consuming fruit and vegetables to prevent cancer is that edible plants contain specific compounds or mixtures of compounds capable to reverse, suppress, prevent or delay either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer ([1]).

This culture has been amply validated by epidemiological studies, with
many intestinal cancers being currently considered as the result of a “non-deficiency malnutrition”. However, little is still known on the mechanism(s) by which phytonutrients prevent cancer, and attempts to translate clinically the results of epidemiological-, cellular-, and animal studies on dietary chemopreventive compounds have so far met with limited
success or with downright failure ([2]).

Indeed, the divide between dietary and clinical studies on cancer prevention has grown steadily. On the one hand, the awareness that fruit and vegetables are associated to a reduced incidence of cancer is well rooted, but, at the same time, there is also a wide acceptance of the skeptic and almost non-scientific view that nutrition is too complex to be summarized into molecular mechanisms of health promotion by single constituents ([3]).

Add also the commercial stakes from the food industry to promote the healthy properties of products enriched with ingredients that consumers can perceive as “cancer preventing”, and the picture could not be more confused and confusing.

Indeed, the study of dietary phytonutrients is complicated. By definition, unlike vitamins and minerals, they are non-essential, with huge differences in individual sensibility to their biological activity. As a result, their beneficial (or detrimental) health effects are statistical in nature and can be observed only in population studies.

Furthermore, the concentration of phytonutrients in food is dramatically altered by culinary processing (pealing, heating, freezing) and by a set of nuances not unlike those that make it possible for wine connoisseurs to distinguish a cheap wine from a precious crue (plant variety, terroir, harvesting time, processing, storing).

Finally, many dietary compounds are extensively modified by phase 1 and phase 2 metabolisms, and are not present in humans in their natural form, but only as metabolites. Laboratory studies have demonstrated chemopreventive activity for several phytonutrients, and especially anthocyanins from berries, procyanidins from grape seeds, phytoestrogens from soy, isothiocyanates from cruciferous plants, epigallocatechin gallate from tea, curcumin from turmeric, and resveratrol from wine [4].

These compounds can modulate gene expression involved in the regulation of cell proliferation, differentiation, and apoptosis, as well as in the suppression of metastasis and angiogenesis. Evidence of clinical activity based on the monitoring of precise biomarkers has been reported for some of these compounds, especially with respect to colon cancer.

Sulforafane from broccoli is the best known chemopreventive isothiocyanate. It is formed from a glucosinolate precursor by enzymatic hydrolysis followed by spontaneous Lossen rearrangement. The enzyme involved (myrosinase) is inactivated by heating, but is expressed also by intestinal bacteria, so that also culinary processed broccoli maintain at
least part of their chemopreventive potential.

Multiple epidemiological, mouse models and cell based studies indicate that broccoliderived Sulforafane may affect the development of various types of cancers and especially prostate tumors.

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see…Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers