The natural compound found in broccoli wakes up the function of a powerful tumor suppressor

Your mother was right: broccoli is good for you. Long associated with a lower risk of cancer, broccoli and other cruciferous vegetables – the plant family which also includes cauliflower, cauliflower, green cabbage, Brussels sprouts and kale – contains a molecule inactivating a gene known to play a role in many human cancers. In a new article published today in Science, researchers, led by Pier Paolo Pandolfi, MD, Ph.D., director of the Cancer Center and the Institute of Cancer Research at the Beth Israel Deaconess Medical Center, demonstrate that gene targeting, known as the WWP1 name, with the ingredient found in broccoli suppressed growth in laboratory animals prone to cancer.

"We have found an important new player that is a critical pathway to the development of cancer, an enzyme that can be inhibited by 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."

A well-known and potent tumor suppressor gene, PTEN is one of the most commonly mutated, deleted, down-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 the 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, the tumor cells exhibit lower levels of PTEN, raising the question of whether the restoration of PTEN activity to a normal level in the context of cancer can trigger the activity suppressive of the tumor of the gene.

To find out, Pandolfi and his colleagues have identified the molecules and compounds that regulate the function and activation of PTEN. By performing a series of experiments on mice and human cells prone to cancer, the team revealed that a gene called WWP1 – also known to play a role in the development of cancer – produces a enzyme that inhibits the suppressive activity of PTEN tumor. How to disable this kryptonite PTEN? By analyzing the physical form of the enzyme, chemists from the research team recognized that a small molecule – formerly called indole-3-carbinol (I3C), an ingredient in broccoli and its – could be the key to calming the carcinogenic effects of WWP1.

When Pandolfi and his colleagues tested this idea by administering I3C to laboratory animals prone to cancer, scientists discovered that the natural broccoli ingredient inactivated WWP1, releasing the brakes of PTEN's tumor suppressor.

But do not head to the farmer's market for the moment; The first author, Yu-Ru Lee, Ph.D., a member of the Pandolfi Lab, notes that you should eat almost 6 kilograms of Brussels sprouts a day – and those who are not – to reap the potential benefit against the cancer. That's why the Pandolfi team is looking for other ways to take advantage of this new knowledge. The team plans to further investigate the operation of WWP1 with the ultimate goal of developing more potent inhibitors of WWP1.

"The genetic or pharmacological inactivation of WWP1 with CRISPR or I3C technology could restore the function of PTEN and further release its tumor suppressor activity," Pandolfi said. "These findings pave the way for a long-sought tumor suppressor reactivation research approach for the treatment of cancer."