Sulforaphane Blocks Prostate Cancer by Stabilizing a DNA Methylation Pathway

SFN is an organosulfur compound that has been found to exhibit anticancer, antidiabetic, and antimicrobial properties in various experimental models. It is obtained from cruciferous vegetables such as broccoli, Brussels sprouts, or cabbages. The enzyme myrosinase transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant (such as from chewing). Young sprouts of broccoli and cauliflower are particularly rich in glucoraphanin.

Investigators at Oregon State University (Corvallis, USA) had shown in previous studies that the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC) enzymes, contributed to the antiproliferative effects of SFN. However, the effects of SFN on other common epigenetic marks such as DNA methylation have not been studied thoroughly.

As promoter hyper-methylation of cyclin D2, a major regulator of the cell cycle, has been shown to correlate with prostate cancer progression, and restoration of cyclin D2 expression exerts antiproliferative effects on prostate cancer cells; the current study was designed to investigate the effects of SFN on the DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in prostate cancer cells.

Results published in the October 26, 2011, issue of the journal Clinical Epigenetics demonstrated the ability of SFN to modulate epigenetically cyclin D2 expression. SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways.

“It appears that DNA methylation and HDAC inhibition, both of which can be influenced by sulforaphane, work in concert with each other to maintain proper cell function,” said senior author Dr. Emily Ho, associate professor of nutrition and exercise sciences at Oregon State University. “They sort of work as partners and talk to each other. With these processes, the key is balance. DNA methylation is a natural process, and when properly controlled is helpful. But when the balance gets mixed up it can cause havoc, and that is where some of these critical nutrients are involved. They help restore the balance.”

“Cancer is very complex and it is usually not just one thing that has gone wrong,” said Dr. Ho. “It is increasingly clear that sulforaphane is a real multitasker. The more we find out about it, the more benefits it appears to have.”

Related Links:
Oregon State University