Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Longitudinal Trial

Long-term Effects Secondary to Cancer Therapy in Adults Clinical Trial

Official title: Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Randomized Longitudinal Trial

Status Recruiting

Clinical Trial Summary

Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancer. Studies identified PEITC and several active isothiocyanates in watercress extract that may have significant anticarcinogenic activity. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes, by inhibiting cell cycle progression and/or by inducing apoptosis.

These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.

Clinical Trial Description

The relation between cancer and nutrition has been well established; cancer builds upon damage to cellular DNA resulting from carcinogenic environmental factors, in which nutrition plays a major role. Many diet and lifestyle factors can influence the development of cancer, a disease expected to affect worldwide more than 1 in 3 people. Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancers at several locations. In 1977, a study in laboratory animals showed the potential effect of phenylethyl isothiocyanate (PEITC) to inhibit carcinogenesis. Recent studies identified several active isothiocyanates in watercress extract that may have more significant anticarcinogenic activity than PEITC alone. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes; e.g. phase II enzymes (quinone reductase, glutathione S-transferases, UDP glucuronosyltransferases);, by inhibiting cell cycle progression and/or by inducing apoptosis.

Several watercress components have antigenotoxic effects in vitro resulting in reduced DNA damage and have anti-proliferative effects. These components include flavonols such as quercetin, hydroxycinnamic acids such as ferulic acid and p-coumaric acid. In HT29 colon cancer cells, an extract of watercress juice was associated with inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis. In MDA-MB-23 human breast cancer cells, watercress extract inhibited metalloproteinase-9 activity, thus suppressing the invasive potential of cancer cells. In breast cancer, epidemiological studies suggest that cruciferous vegetables may reduce cancer incidence. In animal studies, a 9-week PEITC-NAC supplemented diet vs a non-supplemented diet was significantly associated with reduction in tumour size and weight.

A recognised mechanism by which PEITC inhibits the growth and survival of established cancer cells is through the inhibition of angiogenesis. A study explored the impact of PEITC on a specific pathway central to angiogenesis by exposing human MCF7 breast cancer cells to PEITC and measuring hypoxia inducible factor (HIF) signaling activity. PEITC was shown as an effective inhibitor of HIF activity which may contribute to its anti-angiogenic and anti-cancer properties. A follow up to this experiment demonstrated that, similar to PEITC, crude watercress extracts inhibited cancer cell growth and HIF activity in vitro. Furthermore 6 to 8 hours after a significant amount dietary intake of watercress by four healthy participants, peripheral blood cells demonstrated significantly reduced HIF signalling activity, suggesting that dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway.

Of further relevance, a blind, randomized crossover study was carried out in 60 healthy volunteers instructed to consume one pack (85g) of raw watercress daily for 8 weeks. Compared to the control phase, watercress supplementation increased lymphocytes' DNA resistance to free radicals, thus reducing DNA damage. The hypothesis set out was that watercress may reduce cancer risk via decreased damage to DNA and possible effects on antioxidant status by increasing levels of plasma carotenoids.

These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence, a not yet explored area. Of note, that the role of nutrition intervention in medium and long term outcomes in cancer has been demonstrated. It is today acknowledged as grade A evidence that individualized nutritional counseling and education plays a central role in improving long-term outcomes in cancer, by prolonging survival, reducing late RT toxicity and improving QoL. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis. ;

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Outcomes Assessor)

Related Conditions & MeSH terms

• Long-term Effects Secondary to Cancer Therapy in Adults

• NCT number: NCT02468882
• Study type: Interventional
• Source: University of Lisbon
• Contact: Paula Ravasco, MD PhD
• Email: p.ravasco@medicina.ulisboa.pt
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2014
• Completion date: January 2019