Compound found in broccoli, kale may be a new therapeutic option for treating cancer

DELHI: A natural compound found in broccoli, kale, and other cruciferous vegetables may keep cancer at bay by activating a tumor suppressor gene, suggests a recent study.

Our body has its own defense mechanism to fight cancer, but sometimes these mechanisms become weak to suppress tumor growth leading to cancer. Now, the study published in the journal Science demonstrated that indole-3-carbinol (I3C) -- a compound found in cruciferous vegetables such as broccoli, cabbage, kale, and cauliflower impeded tumor growth in a mouse model of prostate cancer. I3C promotes PTEN, a tumor suppressor protein whose activity is often decreased in human cancers, explain the authors.

Reactivation of the tumor suppressor PTEN may provide a strategy for battling tumors.

Pier Paolo Pandolfi, Director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess Medical Center, and colleagues sought to identify upstream regulators of PTEN dimerization and membrane localization, inhibition of which may restore PTEN activity and provide therapeutic opportunities against cancer.

"We found a new important player that drives a pathway critical to the development of cancer, an enzyme that can be inhibited with a natural compound found in broccoli and other cruciferous vegetables," said Pandolfi. "This pathway emerges not only as a regulator for tumor growth control but also as an Achilles' heel we can target with therapeutic options."

PTEN, a well-known and potent tumor suppressive gene, is one of the most frequently mutated, deleted, down-regulated or silenced tumor suppressor genes in human cancers. Certain inherited PTEN mutations can cause syndromes characterized by cancer susceptibility and developmental defects. But because the complete loss of the gene triggers an irreversible and potent failsafe mechanism that halts 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, tumor cells exhibit lower levels of PTEN, raising the question of whether restoring PTEN activity to normal levels in the cancer setting can unleash the gene's tumor suppressive activity.

Carrying out a series of experiments in cancer-prone mice and human cells, the team revealed that a gene called WWP1 -- which is also known to play a role in the development of cancer -- produces an enzyme that inhibits PTEN's tumor suppressive activity. How to disable this PTEN kryptonite? By analyzing the enzyme's physical shape, the research team's chemists recognized that a small molecule -- formally named indole-3-carbinol (I3C), an ingredient in broccoli and its relatives -- could be the key to quelling cancer-causing effects of WWP1.

When Pandolfi and colleagues tested this idea by administering I3C to cancer-prone lab animals, the scientists found that the naturally occurring ingredient in broccoli inactivated WWP1, releasing the brakes on the PTEN's tumor suppressive power.

"Either genetic or pharmacological inactivation of WWP1 with either CRISPR technology or I3C could restore PTEN function and further unleash its tumor suppressive activity," said Pandolfi. "These findings pave the way toward a long-sought tumor suppressor reactivation approach to cancer treatment."

For detailed study log on to DOI: 10.1126/science.aau0159