Nutrition Frontiers - Winter 2018

Volume 9, Issue 1

Date Posted: 

Wednesday, February 14, 2018

Dear Nutrition Enthusiast,

This issue showcases the chemopreventive activity of sulforaphane, how a high fat, high cholesterol diet may impact hepatocellular carcinoma, and p53 activation from benzyl isothiocyanate. Meet our spotlight investigator, Dr. John Groopman, and his research on detoxication of air pollutants with a broccoli supplement. Learn about miso, the buttery probiotic, upcoming announcements and more.


Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane

An image of cruciferous vegetablesIn a study by Bauman and colleagues, in vitro and in vivo models and a pilot clinical trial investigated the potential chemopreventive activity of sulforaphane, a phytochemical found in cruciferous vegetables, against oral environmental carcinogenesis. In 10 healthy volunteers, they evaluated the bioavailability and effects on a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor signaling in oral epithelium of ingesting beverages with glucoraphanin-rich broccoli sprout extract (BSE) or sulforaphane-rich BSE, or topical sulforaphane-rich BSE. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Ingestion of either beverage demonstrated preliminary evidence of NRF2 pathway activation in oral mucosa. In in vitro models, sulforaphane treatment of 4 head and neck squamous cell carcinoma cell lines, and Het-1A, a normal mucosal epithelial cell line, led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. In an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO), sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors. Further clinical investigation will clarify the potential chemopreventive potential of BSE.


The Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) is now accepting applications for the Mary Frances Picciano Dietary Supplement Research Practicum taking place on May 30-June 1, 2018, at the NIH campus in Bethesda, MD. The deadline to apply is March 12, 2018.

Upcoming Events

March 13, 2018
Diet and Cancer Prevention: Chewing on the Human Complexities lecture by Dr. Johanna Lampe, Stars in Nutrition and Cancer lecture series (available as archive following lecture).

April 13-15, 2018
Oncology Nutrition DPG Symposium
Minneapolis, MN

April 14-18, 2018
AACR Annual Meeting: Driving Innovative Cancer Science to Patient Care
Chicago, IL

May 1-2, 2018
Defining Precision Nutrition Symposium
Kannapolis, NC


Dietary Fat/Cholesterol: Potential Role in NASH/HCC Axis

An image of fatty foods, including hamburger, fries, and pizza.A high-fat and high-cholesterol (HFHC) diet has been shown to induce nonalcoholic steatohepatitis (NASH) and progression to hepatocellular carcinoma (HCC) in animal models. Huang and colleagues examined if hepatic protein kinase C beta (PKCβ) deficiency and retinoblastoma (RB) protein expression were functionally linked in Wild Type and PKCβ-/- mice fed a HFHC diet. They also compared PKCβ expression in HCC versus normal tissue. They observed diet-induced hepatic PKCβ expression was accompanied by a time-dependent increase in phosphorylation of Ser780 RB protein, suggesting diet-responsive signaling pathways play a role in RB protein levels. PKCβ-/- livers exhibited reduced protein levels despite increased transcription of the RB gene. It also was accompanied by reduced RBL-1 with no significant effect on RBL-2 protein levels. The findings suggest that PKCβ may play a role in controlling phosphorylation and modulating the stability of cell cycle associated proteins in cholesterol metabolism and may be an early event that impacts the progression of diet-induced HCC.  Further studies may explore the potential of diet-induced PKCβ expression as a pharmacologic intervention in the suppression of tumorigenesis.

Benzyl Isothiocyanate-Mediated p53 Activation

An image of outstreched hands holding a breast cancer awareness pink ribbonTumor suppressor p53 is the most commonly silenced or mutated gene in cancer and plays a critical role in suppressing growth, angiogenesis, invasion and migration, apoptosis, and growth inhibition. Mice models have shown the functional relevance of reconstitution of p-53 pathway to inhibit growth and progression of established tumors. Xie and colleagues aimed to achieve p53-activation using benzyl isothiocyanate (BITC), an isothiocyanate capable of inhibiting chemically-induced cancer in animal models. Specifically, they examined how BITC-mediated activation of tumor-suppressors p53 and p73 leads to growth-inhibition of breast cancer cells. They found strong evidence that BITC-induced p53 and p73 axes converge on tumor-suppressor liver kinase B1 (LKB1), transcriptionally upregulating LKB1 in p53-wild-type and p53-mutant cells, respectively. They uncovered that BITC modulates tumor-suppressors p53 and p73 and LKB1 and not only activates p53 signaling networks in p53-wild-type breast cancer but also functionally restores p53-signaling in p53-mutant breast cancer. These data provide insight of the integral role of the crosstalk between BITC, p53/LKB1 and p73/LKB1 axes in breast tumor growth-inhibition.


Portrait of John D. Groopman, PhDJohn Groopman, PhD is the Edyth H. Schoenrich Professor of Preventive Medicine in the Johns Hopkins University Bloomberg School of Public Health. He is also Professor of Oncology and Associate Director of the Cancer Center for Population Sciences at Johns Hopkins School of Medicine and Sidney Kimmel Comprehensive Cancer Center. For 20 years he served as Chair of the Department of Environmental Health Sciences at the Johns Hopkins University Bloomberg School of Public Health. Dr. Groopman received his doctoral degree at MIT. His research involves the development and application of molecular biomarkers of exposure, dose, and effect from environmental carcinogens, including carcinogens naturally occurring in the diet. A major emphasis of his research has been the elucidation of the role of aflatoxins in the induction of liver cancer in high-risk populations living in Asia and Africa. John was awarded an R01, Detoxication of Air Pollutants in Humans with a Broccoli Supplement.

Read more about John Groopman

Did You Know? Miso:  The “Buttery” Probiotic

A bowl of miso soup on a table.Miso is a high protein fermented soybean paste rich in probiotics and used to make Miso soup, a staple of the Okinawan diet. In the West, miso is often compared to peanut butter and described as “that used as butter” for its smooth texture.  Miso is created using the ancient two-step fermenting process that typically begins with inoculating steamed rice with Aspergillus oryzae mold culture and incubating for about 48 hours to create koji. Koji serves as a source of enzymes to break down proteins, starches, and fats into easily digested amino acids, sugars, and fatty acids. Other grains and legumes can be used to make a variety of different types of koji.  Next, koji is cooked with soybeans, salt, water, and seed miso and stored in large vats for at least 6 to 36 months.  During this process, lactic acid bacteria and yeast transform simple sugars into organic acids and alcohols that lead to a variety of rich flavors and aromas of miso.

Rule of thumb, the shorter the fermentation process, the milder the flavor and the whiter the miso.  Slightly longer fermentation produces a stronger yellow miso. Red miso results from the longest fermentation and offers a more umami and meatier flavor along with a hearty pungent aroma. Next time you reach for a condiment consider a dollop of the versatile miso to add flavor to your dressings, marinades, sauces, hummus or Greek yogurt in addition to the traditional miso soup.

Miso Soup Tips:

  1. Consider a ratio of 1 Tbsp. of miso to 1 – 1 ½ cups of water and dissolve miso to taste with warm water to avoid clumps of miso.
  2. Experiment with the variety of miso from Shiro miso (white miso), Shinshu miso (yellow miso) or Aka miso (red miso).
  3. Avoid adding it to boiling water, which will kill the probiotics in miso. Wait until the soup has been taken off the heat, then stir or whisk in miso to taste.