Trygve Tollefsbol, PhD, DO

Professor of Biology
Senior Scientist, Comprehensive Cancer Center, Comprehensive Center for Healthy Aging, and Comprehensive Diabetes Center
Nutrition Obesity Research Center
Director and Founder, Cell Senescence Culture Facility
Lead Editor and Founder, Elsevier’s Translational Epigenetics Series
The University of Alabama at Birmingham, Birmingham, AL

image of Dr. Trygve Tollefsbol
Abstract: Interest in cancer epigenetics has arisen from the fact that epigenetic processes affect many aspects of tumor formation and progression. The reversibility of epigenetic changes that may arise in early tumorigenesis is an important aspect of their potential in approaches for cancer prevention. We coined the term “epigenetics diet” only 6 years ago based on numerous studies delineating the impact of bioactive dietary compounds on changes in the epigenome. There is aberrant gene expression due to epigenetic changes in all cancer types, so an approach to cancer therapy would be to use these bioactive dietary compounds as a means of not only neutralizing epigenomic aberrations as cancer treatment, but also cancer prevention. Although many of these phytochemicals are efficacious alone or in combination, some are only efficacious at considerably high doses not achievable by diet alone. Combinatorial studies are important to enhance our understanding of the interactions between various epigenomic-modifying dietary compounds. Compounds that display anticancer properties by themselves may act in an additive, synergistic, or even antagonistic manner in combination. The epigenetic mechanisms for these interactions are not fully understood, and are an area of increasing interest for the studies of the epigenetics diet. For instance, have found that both (-)-epigallocatechin-3-gallate (EGCG) from green tea and sulforaphane (SFN) from cruciferous vegetables are able to down-regulate telomerase in breast cancer cells. This occurs through epigenetic modifications of the promoter region of hTERT, the gene that encodes the catalytic subunit of telomerase. Since telomerase promotes tumor formation and is active in about 90% of cancers, this epigenetic inhibition of its catalytic subunit gene may have considerable potential in breast cancer prevention. Our studies also indicate that these bioactive dietary compounds are able to convert estrogen-receptor (ER)-negative breast cancer cells to ER-positive breast cancer cells treatable with tamoxifen or to prevent the formation of highly lethal ER-negative breast cancer. This occurs through epigenetic modifications of the ERα gene in response to EGCG and SFN. The components of the epigenetic diet are effective both in vitro and in vivo and also appear to be more effective when administered early in life. On the horizon for studies on the epigenetics diet and cancer prevention are additional combinatorial studies to prevent cancer, studies on the effects of the epigenetics diet on the gut microbiome and cancer prevention and early-life analyses of the impact of the epigenetics diet on cancer prevention as well as many other areas of study.