A team of scientists from the US and China have discovered that grape-seed extract kills laboratory leukemia cells by making them commit suicide, thus showing the potential value of natural compounds in the treatment of cancer.

The study was the work of lead author, Dr Xianglin Shi, professor in the Graduate Center for Toxicology at the University of Kentucky and colleagues and is published online in the 1 January 2009 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.

A number of studies have already revealed that eating fruit and vegetables helps to prevent cancer, and that this is likely due to the presence of proanthocyanidins. Shi and colleagues have already investigated this family of antioxidant compounds in apple peel and found it triggered cell death in cancer cells but not non-cancer cells.

Studies on grape seed extract have also suggested that it reduces breast tumors in rats and skin tumors in mice, and is active in a number of laboratory human cancer cell lines (such as skin, breast, colon, lung, stomach and prostate cancer cells), but until now nobody has investigated its effect on blood cancers.

Shi and colleagues used a commercially available grape seed extract and exposed leukemia cells to various concentrations of the extract for 12 and 24 hours, and also looked at what happened when leukemia cells were exposed to 50 µg/mL of the extract over various time intervals.

The results showed that exposure to grape seed extract resulted in dose and time-dependent increase in cancer cell apoptosis. They also discovered that the extract did not affect normal cells but they weren’t able to determine why.

“This is a natural compound that appears to have relatively important properties,” said Shi.

He and colleagues then examined the underlying mechanisms by which the grape seed extract caused the leukemia cells to commit suicide. They found that the extract had a strong effect on the activation of JNK, which led to the up-regulation of Cip/p21 (a CDK inhibitor which controls the cell cycle).

They double checked their finding by showing that the grape seed extract didn’t work when used with an agent that blocked JNK: this was a pharmacologic approach. And using a genetic approach, they showed that silencing the JNK gene also disabled the grape seed extract’s ability to trigger apoptosis.

Shi told the press that:

“These results could have implications for the incorporation of agents such as grape seed extract into prevention or treatment of hematological malignancies and possibly other cancers.”

“What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grape seed extract fits into this category,” he added.

Shi said these finding were not enough to warrant advising advise people to start eating lots of grapes, grape seeds, or grape skin in the hope they will avoid getting cancer. It’s too early to say for sure that grape seed extract has this effect, even though the results are promising, he said.

Killing cancer cells in a test tube is not the same as treating tumors in live subjects.

In the US, hematological cancer like leukemia, lymphoma and myeloma accounted for over 118,000 new cases and nearly 54,000 deaths in 2006.

“Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase.”
Ning Gao, Amit Budhraja, Senping Cheng, Hua Yao, Zhuo Zhang, and Xianglin Shi
Clin Cancer Res Vol 15, Issue 1, pages 140-149, Published 1 January 2009
doi: 10.1158/1078-0432.CCR-08-1447

Click here for Abstract.

Sources: Journal abstract, American Association for Cancer Research.

Written by: Catharine Paddock, PhD