Mechanisms for inhibition of colon cancer cells by sulforaphane through epigenetic modulation of microRNA-21 and human telomerase reverse transcriptase (hTERT) down-regulation.
Curr Cancer Drug Targets. 2017 Feb 5. Epub 2017 Feb 5. PMID: 28176652
Samantha L Martin
Epigenetic modulations such as histone modifications are becoming increasingly valued for their ability to modify genes without altering the DNA sequence. Many bioactive compounds have been shown to alter genetic and epigenetic profiles in various forms of 6 cancers. Of the many dietary phytochemicals, sulforaphane (SFN), found in cruciferous vegetables such as kale, cabbage and broccoli sprouts, has been present as one of the most potent (histone deacetylase) HDAC inhibitors to date. Recently, it has been 9 identified that HDAC inhibitors may play a vital role in regulating microRNAs (miRNAs) in many human cancers. Specifically, studies have reported that oncogene microRNA-21 (miR-21) is dysregulated in many forms of cancer, especially colorectal 12 cancer cells (CRC). Accordingly, we evaluated the molecular mechanism of dietary SFN in CRC and its impact on the regulatory gene of telomerase, human telomerase reverse transcriptase (hTERT), which is elevated in 90% of cancers and essential for their 15 continued proliferation. We demonstrated the effects of physiologically relevant concentrations of dietary SFN in both HCT 116 and RKO CRC cells, and showed for the first time that SFN treatment decreased cell density, significantly inhibited cell viability 18 and induced apoptosis of CRC cells. Our results suggest that SFN regulates mRNA levels by inhibition of HDAC1. We also demonstrate that SFN down-regulated miR-21, telomerase protein and enzymatic activity in RKO CRC cells. These findings suggest that 21 hTERT down-regulation by HDAC1 inhibition is a promising approach for delaying and/or preventing CRC and may be accomplished via consumption of SFN in cruciferous vegetables.