• No se han encontrado resultados

4.7 Conclusiones Parciales

5.1.1 Una barrera de fonones

In recent years, several epidemiological studies have suggested that isothiocyanates resulting from the hydrolysis of alkyl glucosinolates found in cruciferous vegetables may play a chemoprotective role in the human diet by reducing the risk of cancer (Hecht, 2000).

A review of anticancer effects of glucosinolates highlights several points where studies can disagree, in particular, the spectrum of anticancer activities. Epidemiological evidences suggested "possible" health benefits rather than a particular activity, which is limited to lung and gastric cancer and not proven to be for all types of cancers by the uptake of a specific subtype of vegetables with critical type and amount of phytochemicals. In addition, they emphasized the role in humans of polymorphism for the genes responsible for glutathione S-transferase (GST) enzymes that are responsible for detoxification process for carcinogenic factors, which in turn reduces the risk of cancer and ageing progresses. Different individuals express these genes differently, thus altering their susceptibility for cancer by affecting their responses to cancer “chemoprotective” food (Kim and Park, 2009).

Investigations showed that the anti-cancer effect is not the same with all glucosinolates and their catabolic products, but is dependent on the nature of the side chain of the parent glucosinolate (Schonhof et al., 2004). Studies to compare the health promoting effects of individual products derived from glucosinolate myrosinase hydrolysis; the most important of which are sulforaphane (SF) and indole-3-carbinol (I3C) (Borowski et al., 2008), versus the effect of a whole plant extract containing their precursor glucosinolates, glucoraphanin and glucobrassicin respectively, are the focus of clinical research aiming to find potential cancer preventing and treatment compounds. The pathways triggered by SF and I3C are different, and thus studying the interaction between SF and I3C in an extract, on their effect on any cancer type is still an area of interest for researchers, as a possible synergetic activity for their anti-inflammatory effect is expected (Jeffery and Araya, 2009). Different mechanisms of action were proposed for the chemoprotective catabolic product I3C present in broccoli, cabbage, Brussels sprouts and cauliflowers, which has been proved to be successful against respiratory papilloma, and both breast and cervical cancer through inhibition of transcription of estrogen- responsive genesstimulated by 17ß-estradiol, as well as by its condensation product, 3,3’-diindolymethane (DIM), which is produced under acidic pH. These were found to have not only a preventive effect, but also therapeutic treatment for prostate cancer. In anin vivo study, mice inoculated with prostate cancer cells, and injected intraperitoneally with I3C (20 mg/ kg body weight), three times a week for 14 days before and after transplantation of prostate cancer cells, showed inhibition of cell growth (78% decrease in tumour volume) byinduction of apoptosisandinhibition of cell proliferation (Souli et al., 2008). The ability of I3C to induce cytochrome enzymes responsible for Phase II detoxification, and unfortunately, also as inducer

for Phase I enzymes, which are known to be responsible for activation of carcinogenesis were also studied (Bellostas et al., 2007a).

SF the isothiocyanate catabolic product derived from sulfur containing glucosinolates such as glucoraphanin present in broccoli sprouts, broccoli, cabbage and Brussels sprouts, was found to be a powerful inducer of phase IIand an inhibitor of phase I

cellular enzymes. In addition, it hasantioxidant activityand the ability toinduce cell apoptosis as well as itsanti-inflammatory activity, andantibacterial activity against

Helicobacter pylori. Other hydrolysis products derived from different aliphatic glucosinolates, including iberin from glucoiberin, erucin from glucoerucin, crambene from epi-progoitrin and allyl isothiocyanate from sinigrin, were all found to have anticancer activity similar to SF, and strongly correlated to their R side-chain structure (Cartea and Velasco, 2008; Higdon et al., 2007).

Isothiocyanates derived from aromatic and aliphatic glucosinolates were found to be different in their anti-cancer activity, which is related to their side-chain structure. Secondary metabolites derived from aromatic amino acids such as gluconasturtiin, the precursor of phenethyl isothiocyanate present in watercress, has demonstrated activity against lung, leukemia, colon, prostate, liver and esophageal cancer (Hecht, 2000; Kim and Park, 2009). Benzyl isothiocyanate derived from glucotropaeolin found in cabbage, garden cress and Indian cress, has been studied for its chemoprotective activity. They showed the ability toinduce cancer cell apoptosisas well as their ability to induce phase II cellular enzymesor toinhibit phase I cellular

enzymes (Cartea and Velasco, 2008; Higdon et al., 2007; Pappa et al., 2006).

The effects of cooked and autolysed Brussels sprouts extracts, which are rich in sinigrin were investigated and the results revealed an inhibition activity for DNA

through scavenging oxygen radicals, and to a lesser extent through induction of

phase II enzymes. The results showed that both cooked and autolysed Brussels

sprouts extracts had almost the same inhibition activity (38%) at concentrations of 10 µg/ mL and 5 µg/ mL respectively. The hydrolysis product, the isothiocyanate derived from sinigrin was at higher concentrations in the autolysed plant extracts (Zhu and Loft, 2001).

Comparison of the cell growth inhibition activity of SF, phenethyl isothiocyanate, I3C and DIM on human colon cancer cell lines has been studied (Pappa et al., 2006). The half-maximal inhibitory concentration (IC50) in cell lines were: 15 mµM for SF and 10 mµM for phenethyl-isothiocyanate, I3C and DIM after 24 and 48h. The study found isothiocyanate to be cytotoxic, whereas indoles acted in a cytostatic manner.

Documento similar