Broccoli contains an ingredient that could target the "Achilles’ heel" of cancers

By Dr. Ananya Mandal, MDMay 19 2019

A new study from the Beth Israel Deaconess Medical Center has found that broccoli, Brussels sprouts, kale, cauliflower, cabbage and collard greens contain a substance that could inactivate a vital gene that plays a role in cancers. Their study titled, “Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway,” was published in the latest issue of the journal Science.

The authors led by Pier Paolo Pandolfi, Director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess Medical Center, write that there have been numerous studies that show the cancer-protective effects of broccoli and other members of the family including cruciferous vegetables. They contain a substance that targets a gene called the WWP1 and thus in lab animals they were shown to suppress tumour growth. Pandolfi in a statement said, “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. This pathway emerges not only as a regulator for tumor growth control, but also as an Achilles' heel we can target with therapeutic options.”

Cancer-protective effects of broccoli. Image Credit: Pakhomov Andrey / Shutterstock

Potent tumor suppressive gene, PTEN, the team explains is a common tumour suppressor gene that commonly undergoes mutations and is deleted or down regulated or silenced. This means that this gene is unable to stop the onset and progression of the cancers. Persons who inherit a mutated version of this gene have a greater risk of getting cancers as well as developmental defects. Each individual carries two copies of the gene – each from either parent. If they carry one defective suppressor gene the activity of PTEN might be reduced. Researchers speculated that if they could increase the activity of the existing PTEN, they could suppress the tumours or cancers. Aiming at finding molecules that could regulate and increase PTEN activity the team set on carrying series of experiments on cancer susceptible lab mice and on human cells in the lab.

The researchers found a gene called the WWP1 that plays a role in development and growth of cancers. This gene produces an enzyme which was found to stop the protective or tumour suppressive actions of PTEN. The team then noted that indole-3-carbinol (I3C) – a component of broccoli could inhibit the effects of WWP1 and thus protect the PTEN activities that suppress the tumour. Pandolfi and colleagues then administered I3C to lab animals that were susceptible to cancer and noted that this allowed PTEN to protect the animals from cancer.

Yu-Ru Lee, PhD, researcher at the Pandolfi lab, who is the first author of the study said that the amount of the molecule needed to provide anticancer benefits would be around 6 pounds of raw Brussels sprouts a day to achieve same levels of the molecule’s dose as in the lab mice. However the authors of the study assure that this knowledge or the key to potentiating PTEN is the big news from this study. They hope that research in this area would soon unlock medicines that target PTEN and potentiate its action as a protector against cancer.

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

Authors of the study wrote in conclusion, “These findings pave the way toward a long-sought tumor suppressor “reactivation” approach to cancer treatment... PTEN impairment is widely pervasive in various human cancers, targeting this pathway toward PTEN reactivation may represent an “Achilles heel” of broad application”

The study received support from the National Institutes of Health.

Beneficial properties of ingredients of broccoli, especially sulforaphanes

Recently researchers from the Czech Republic recently looked at beneficial effects of the ingredients of broccoli. Their study, “Isothiocyanate from Broccoli, Sulforaphane, and Its Properties,” was published in February 2019 in the Journal of Medicinal Food.

The authors of the study write about the molecule “sulforaphane” which is an isothiocyanate that is stored in the form of glucoraphanin within cruciferous vegetables such as broccoli, broccoli sprouts, cauliflower, cabbage and kale. They explain that the glucoraphanin in the plants in converted to sulforaphane using an enzyme called myrosinase.

They reviewed the studies that explored the anti-cancer and cancer protective properties of sulforaphane. They also speculate the sulforaphane can help in other diseases such as osteoporosis, heart and circulatory disease and autism as well.

Efficacy of sulphoraphane in Triple negative breast cancers

In other related research a team led by Nadia Castro from the Tumor Growth Factor Section, Mouse Cancer Genetics Program, NCI, Frederick, Maryland and colleagues in March this year published the results of their work titled, “Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitroand In vivo” in the journal Cancer Prevention Research (Philadelphia Pa.).

They found that sulphorane found is broccoli could benefit women with a specific type of breast cancer called “Triple Negative Breast cancer” or TNBC. They studied the effects of this molecule of cancer-stem like cells or CSC that were isolated from patients and used in labs. They initiated the cancer in lab mice that were given daily injections of 50 mg sulforaphane/kg for 5 and 3 weeks, respectively. They noted that the TNBC cells having self renewal properties were inhibited by the sulforaphane. The authors found that this molecule targeted “Cripto-mediated oncogenic signaling pathway” in order to achieve this tumour inhibition.

Results revealed that suoforaphane was capable of inhibiting proliferation of cells and also stopped the CSC cells from growing. The authors concluded from the study that, “findings indicate that sulforaphane (50 mg/kg) suppresses mammary tumor development in a TNBC animal model, possibly by targeting a CSC population... collective results in this study suggest that the use of sulforaphane for chemoprevention of TNBC is plausible and warrants further clinical evaluation.”