It has been found that a compound called indole-3-carbinol (I3C), present in broccoli and kale, impeded tumor growth in a mouse model of prostate cancer.
The team has also found a molecular pathway for which the protein WWP1 alters and weakens the tumor suppressant PTEN. WWP1 is active in several human cancers. But, their investigation reveals that I3C can inactivate WWP1 by switching off its gene. This unleashes the full power of PTEN to restrict tumor growth.
“We found a new important player that drives a pathway critical to the development of cancer,” says senior study author Dr. Pier Paolo Pandolfi, Director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess Medical Center.
There are more than 100 types of cancer, each depending on the type of cell that it starts in, for which scientists have also identified six hallmarks of cancer at the cell level. These work by sustaining growth signals, avoiding tumor suppression, escaping cell death, promoting endless replication, setting up a blood supply, and triggering invasion and spread.
Previous studies have identified cancer-fighting compounds in cruciferous vegetables, such as cabbage, kale, broccoli, and Brussel sprouts They have suggested that the compounds operate on genes that promote some of the hallmarks of cancer.
The recent study adds to this knowledge. The team already knew that PTEN is normally a powerful tumor suppressor. However, in cancer, the protein’s gene can be absent, altered, down-regulated, or silent.
It is rare for the gene to be absent altogether; that would require the deletion of both of the two copies that each person carries. Often, what happens is that tumors have low levels of PTEN protein, because, for instance, only one of the two copies is active.
This led Dr. Pandolfi and his team to wonder if there might be a way to restore PTEN to its full tumor-suppressing potency, and the extent to which this might stop tumors from growing. To investigate these questions, they set out to pinpoint the molecular pathways that activate PTEN.
Using human cancer cells and a mouse model of prostate cancer, they identified that the protein that WWP1 codes for reduces PTEN’s ability to suppress tumors. Further investigation into WWP1’s molecular shape and biochemical activity revealed that the small molecule I3C was a “natural and potent WWP1 inhibitor.”
However, the team is not suggesting that eating lots of cruciferous vegetables could have the same effect. For a start, a person would have to eat around 6 pounds of raw sprouts per day to reach an effective level of I3C.
Instead, Dr. Pandolfi and his colleagues are looking for other ways to use this knowledge. They are going to continue examining how WWP1 works and whether there might be other molecules with even greater power to block it. “These findings pave the way toward a long-sought tumor suppressor reactivation approach to cancer treatment,” says Dr. Pandolfi.