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Your mother was right. Broccoli is good for you.
Long associated with a lower risk of cancer, broccoli and other cruciferous vegetables, this family of plants also includes cauliflower, cauliflower, green cabbage, Brussels sprouts and kale, and contains a molecule inactivating a gene known to play a role in a variety. common human cancers. In a new article published today in Science, researchers, led by Pier Paolo Pandolfi, MD, PhD, director of the Center Against Cancer and the Institute of Cancer Research at the Beth Israel Deaconess Medical Center, demonstrate that targeting the gene, known as WWP1, with the ingredient found in broccoli prevents tumor growth in cancer prone laboratory animals.
"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, PhD, a member of the Pandolfi Lab, notes that you should eat almost 6 kilograms of Brussels sprouts a day – and those who are not – for the potential benefit of 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."
In addition to Pandolfi and Lee, the authors include, Ming Chen, Jonathan D. Lee, Jinfang Zhang, Tomoki Ishikawa, Jesse Katon, Yang Zhang, Yulia V. Shulga, Assaf Bester, Jacqueline Fung, Emmanuele Monteleone, Lixin Wan. John G. Clohessy and Wenyi Wei, all of BIDMC; Shu-Yu Lin, Chiang Shang-Yin and Chen-Ruey Hwa from the Institute of Biological Chemistry; Tian-Min Fu and Chen Shen from the Harvard Medical School; Chih-Hung Hsu, Hao Chen and Hao Wu from the Boston Children's Hospital; Antonella Papa from the Monash University; Julie Teruya-Feldstein from the Icahn School of Medicine at Mount Sinai; Suresh Jain of Intonation Research Laboratories; and Lydia Matesic from the University of South Carolina.
This work was funded by the National Institutes of Health (R01CA82328 and R35 CA197529), assigned to Pandolfi. Lee benefited in part from the support of the Postdoctoral Fellowship Scholarship, the National Taiwan Science Council and the Postdoctoral Fellowship of the Prostate Cancer Research Program. DOD (PCRP) (W81XWH-16-1-0249).
Disclosures: Pandolfi, Wei and Suresh Jain are co-founders of Rekindle Pharmaceuticals. The company is developing new therapies for cancer. All other authors do not declare any conflict of interest.
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