Introduction
Broccoli and other cruciferous vegetables, which have long been associated with decreased risk of cancer, contain a molecule that inactivates a gene that plays a role in various common human cancers. A new study, led by Pier Paolo Pandolfi, shows that targeting the gene, referred to as WWP1, with the ingredient in broccoli suppressed the growth of tumors in cancer-prone lab animals.
Broccoli
Case study
According to Pandolfi, they had found a new important player that drives a pathway vital to the development of cancer. It is an enzyme that can be inhibited with a natural compound found in broccoli, plus other cruciferous vegetables. This pathway emerged as a tumor growth regulator and also as an Achilles’ heel that can be targeted with therapeutic options.
PTEN is among the frequently mutated, down-regulated, deleted, or silenced tumor suppressor genes in human cancers. Some inherited PTEN mutations can cause syndromes characterized by cancer, developmental defects, and susceptibility. Both copies of the genes (from both parents) are rarely affected because the total loss of the gene triggers a potent fail-safe and irreversible mechanism that stops the proliferation of cancer cells. Tumor cells have lower levels of PTEN. It leads to the question of whether restoring PTEN activity to normal levels can unleash the gene’s tumor-suppressive activity.
Pandolfi and his team identified molecules and compounds that regulated PTEN function and activation. They carried out various experiments in human cells and cancer-prone mice. They revealed a gene known as WWP1 produced an enzyme that inhibited PTEN’s tumor suppressive activity. To disable the PTEN kryptonite, the researchers analyzed the enzyme’s physical shape and noticed that a small molecule could be the key to stopping WWP1’s cancer-causing effects.
When Pandolfi and his team tested this idea by the administration of I3C to cancer-prone lab animals, they discovered that the naturally occurring component in broccoli inactivated WWP1, and released the brakes on the PTEN’s tumor suppressive power.
Conclusion
According to Yu-Ru Lee, PhD, you should not head to the farmers’ market yet. You have to eat close to 6 pounds of Brussels sprouts a day to benefit from their anti-cancer benefit. This is why Pandolfi’s team is looking for other ways to use this new knowledge. They plan to study further the WWP1 function to develop more potent WWP1 inhibitors. Pandolfi said that either pharmacological or genetic inactivation of WWP1 with either I3C or CRISPR technology could restore PTEN function and unleash further tumor suppressive activity. These findings are paving the way toward a long-sought tumor suppressor reactivation approach to cancer treatment.
References
Lee, Y.-R., Chen, M., Lee, J. D., Zhang, J., Lin, S.-Y., Fu, T.-M., Chen, H., Ishikawa, T., Chiang, S.-Y., Katon, J., Zhang, Y., Shulga, Y. V., Bester, A. C., Fung, J., Monteleone, E., Wan, L., Shen, C., Hsu, C.-H., Papa, A., Clohessy, J. G., Teruya-Feldstein, J., Jain, S., Wu, H., Matesic, L., Chen, R.-H., Wei, W., & Pandolfi, P. P. (2019). Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC–WWP1 inhibitory pathway. Science, 364(6441), eaau0159. https://doi.org/10.1126/science.aau0159
Mitchell, J. (2019, May 16). Natural compound found in broccoli reawakens the function of potent tumor suppressor. Beth Israel Deaconess Medical Center. https://www.bidmc.org/about-bidmc/news/2019/05/broccoli-reawakens-tumor-suppressor
