|Khan, Shabana -|
|Aumsuwan, Pranapda -|
|Khan, Ikhlas -|
|Walker, Larry -|
|Dasmahapatra, Asok -|
Submitted to: Chemical Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 12, 2011
Publication Date: October 12, 2011
Citation: Khan, S.I., Aumsuwan, P., Khan, I.A., Walker, L.A., Dasmahapatra, A.K. 2011. Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome. Chemical Research in Toxicology. 25:61-73. Interpretive Summary: Breast cancer accounts for ~30% of all cancers diagnosed in the United States, and it is the second leading cause of cancer death in women. Extensive research has been done to find out the mechanisms of breast cancer development and their preventions, however, the results are still remained inconclusive. Both genetic and epigenetic mechanisms are involved in the development of breast cancer. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in reversing some of these defects observed in breast cancer. Many studies have been focused on linking diet (such as soy rich diet) with breast cancer prevention. Dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, isothiocyanates from plant foods, curcumin from turmeric, resveratrol from grapes, and sulforaphane from cruciferous vegetables have the potential to modulate the epigenetic events associated with breast cancer. This approach could facilitate the discovery and development of novel drugs for the treatment of breast cancer. In this brief review, we have focused on major epigenetic events associated with breast cancer and discuss the potency of bioactive dietary components as epigenome modifiers that afford new therapeutic or preventive approaches for breast cancer.
Technical Abstract: Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in reversing some of these defects. Methylation of CpG islands is an important component of the epigenetic code and a number of genes become abnormally methylated in breast cancer patients. Currently, several epigenetic-based synthetic drugs that can reduce DNA hypermethylation and histone deacetylation are undergoing preclinical and clinical trials. However, these chemicals are generally very toxic and do not have gene specificity. Epidemiological studies have shown that Asian women are less prone to breast cancer due to their high consumption of soy food than the Caucasian women of western countries. Moreover, complementary/and or alternative medicines are commonly used by Asian populations which are rich in bioactive ingredients known to be chemopreventive against tumorigenesis in general. Examples of such agents include dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, isothiocyanates from plant foods, curcumin from turmeric, resveratrol from grapes, and sulforaphane from cruciferous egetables. These bioactive components are able to modulate epigenetic events and their epigenetic targets are known to be associated with breast cancer prevention and therapy. This approach could facilitate the discovery and development of novel drugs for the treatment of breast cancer. In this brief review, we will summarize the epigenetic events associated with breast cancer and the potential of some of these bioactive dietary components to modulate these events, and thus afford new therapeutic or preventive approaches.