Natural compound found in broccoli awakens the function of a powerful tumor suppressor.
Finding offers potential novel approach to cancer treatment and prevention
Your mother was right. Broccoli is good for you. Long associated with a reduced risk of cancer, broccoli and other cruciferous vegetables - the plant family, which also includes cauliflower, green cabbage, Brussels sprouts and kale - contain a molecule that inactivates a gene known to play a role in many human cancers.
Broccoli for cancer
In a new article published today in Science, researchers led by Pier Paolo Pandolfi, MD, PhD, Director of the Beth Israel Deaconess Medical Center's Cancer Research Centre and Institute, show that targeting the gene, called WWP1, with the ingredient found in broccoli has suppressed tumor growth in laboratory animals with cancer.
"We have found an important new player that is an essential pathway to cancer development, an enzyme that can be inhibited with a natural compound found in broccoli and other cruciferous vegetables," said Pandolfi. "This pathway appears not only as a regulator of tumor growth control, but also as an Achilles' heel that we can target with therapeutic options.
The PTEN gene is a powerful tumor suppressor
A well-known and powerful tumor suppressor gene, PTEN is one of the most frequently mutated, deleted, downwardly regulated or inhibited tumor suppressor genes in human cancers. Some mutations inherited from PTEN can cause syndromes characterized by cancer susceptibility and developmental defects.
But since the total loss of this gene triggers an irreversible and powerful safety mechanism that stops the proliferation of cancer cells, both copies of the gene (humans have two copies of each gene, one from each parent) are rarely affected. Instead, tumour cells have lower levels of PTEN, raising the question of whether restoring PTEN activity to normal levels in the context of cancer can trigger the tumour suppressive activity of this gene.
To find out, Pandolfi and his colleagues identified the molecules and compounds that regulate the function and activation of PTEN. By conducting a series of experiments on mice and human cells prone to cancer, the team found that a gene called WWP1 - also known to play a role in cancer development - produced an enzyme that inhibits the suppressive activity of the PTEN tumor.
The I3C molecule is believed to be the key to calming the carcinogenic effects of WWP1
How to disable this PTEN kryptonite? By analyzing the physical form of the enzyme, the chemists on the research team recognized that a small molecule - formerly called indole-3-carbinol (I3C), an ingredient in broccoli and cruciferae - could be the key to alleviating the carcinogenic effects of WWP1.
When Pandolfi and his colleagues tested this idea by administering the I3C molecule to cancer-prone laboratory animals, scientists discovered that the natural ingredient in broccoli inactivated WWP1, releasing the brakes of PTEN's tumor suppressing power.
But don't go to the farmer's market right now; the first author, Yu-Ru Lee, PhD, a member of the Pandolfi laboratory, notes that you should eat about 6 kilos of Brussels sprouts a day to get the potential benefit against cancer. That's why the Pandolfi team is looking for other ways to take advantage of this new discovery. The team plans to further investigate the functioning of WWP1 with the aim of developing more potent WWP1 inhibitors.
CRISPR technology could restore the function of PTEN
"The genetic or pharmacological inactivation of WWP1 with CRISPR or I3C technology could restore PTEN function and further release its suppressive activity from tumors," said Pandolfi. "These results pave the way for a long-awaited tumor suppressor reactivation research approach for cancer treatment.
