Grape seed extract may stop colorectal cancer spread
stopped the spread of colorectal cancer cells in lab mice, suggests
new research funded by the US National Cancer Institute (NCI).
Interest in grape seed extracts has been increasing, particularly in Europe where half of the world's grape seed extract is said to end up. The health benefits of its grape seed extract have mostly focused on heart health, but there is also evidence of benefits of grape seed extract against skin and prostate cancer. Moreover, the NCI is currently conducting a trial on grape seed extract and women who are disposed to have a higher risk of breast cancer.
The new study, published in the journal Clinical Cancer Research (Vol. 12, pp. 6194-6202), presents data of in vitro and in vivo studies and suggests the extracts may also have benefits in the prevention of colorectal cancer, which accounts for nine per cent of new cancer cases every year worldwide.
Professor Rajesh Agarwal from the University of Colorado Health Sciences Center and lead researcher on the new study said however: "We are not suggesting that people run out and buy and use grape seed extract.
"The value of this preclinical study is that it shows grape seed extract can attack cancer, and how it works, but much more investigation will be needed before these chemicals can be tested as a human cancer… preventive," he said.
The researchers used two cell lines to model human colorectal cancer, LoVo and HT29, and found a dose- and time-dependent inhibition of cell growth. The latter cell-line is representative of relatively late-stage colorectal cancer, said the researchers.
The in vitro data showed that cell growth of the LoVo cells was inhibited by 13 to 58 per cent for grape seed extract doses of 25, 50 and 100 micrograms per millilitre after 24 hours. In HT29 cells, doses on 50 and 100 micrograms per millilitre decreased cell numbers by 36 and 43 per cent, respectively.
The authors also report that the grape seed extract lead to increases in the availability of a critical protein, Cip1/p21, in the tumours. Indeed, levels were found to be more than 150 times higher after 12 hours of grape seed extract exposure. The protein is involved in effectively freezing the cell cycle, and often promotes programmed cell death (apoptosis).
Decreases in a number of different cyclin proteins and associated cyclin-dependent kinases (CDKs) were also measured by the researchers, a result that did not surprise Prof. Agarwal since Cip1/p21 is said to be powerful enough to inhibit the activity of CDKs and can also control apoptosis.
"This protein physically interacts with CDKs," he explained. "In normal cells, it attaches to CDKs to inhibit growth, but if a cell wants to grow, as it does in cancer, levels of Cip1/p21 are reduced, or non-functional."
"Based on the encouraging in vitro anticancer efficacy of grape seed extract against colorectal cancer, we further studied its efficacy in a preclinical animal model by… implantation of HT29 xenograft in… mice," wrote lead author Manjinder Kaur.
Mice were fed a dose of 200 milligrams per kilogram of body weight (a dose larger than a human would reasonably use) and the researchers found that, after eight weeks, the volume of the grafted tumour had decreased by 44 per cent, compared to control mice. No toxic side effects were observed in treated mice, despite the high dose.
The researchers also report that, as was observed in the cell culture studies, Cip1/p21 protein levels increased in the tumours of the grape seed extract-fed mice.
Professor Agarwal and his co-workers called for additional mechanistic studies to fully elucidate the mechanism, in conjunction with dose-dependent in vivo studies to effectively determine the lowest effective doses, as well as the highest non-toxic doses, by which grape seed extract can offer anticancer benefit in mice.
Dr Kat Arney, cancer information officer at Cancer Research UK, told NutraIngredients.com that the research was interesting and added to the current knowledge about the potential anti-cancer properties of grape seed extract.
"But there is still a lot of work to be done before we really understand how this cocktail of chemicals works and if it could ever be used to prevent bowel cancer. One of the best ways to reduce the risk of cancer is to eat a healthy diet, rich in a wide variety of fruit and vegetables -and, of course, not to smoke," she said.
