There are numerous nutrients in garlic that are beneficial and one of its most abundant is an organosulfur compound called S-allylcysteine (SAC). This water-soluble compound has already been reported to inhibit proliferation and induce apoptosis in ovarian cancer cells. However, the exact mechanisms contributing to its antitumor efficacy are not entirely clear. To better understand how SAC reduces cancer cell progression, a group of scientists decided to investigate the epigenetic mechanism involved in the process. Their results were published in the Journal of Ovarian Research.
Ovarian cancer is a leading gynecological cancer that affects more than 22,000 women each year. Unlike other cancers, there are no precise screening tests for OC and it can be difficult to detect in the early stages. For this reason and others, the prognosis for many ovarian cancer patients is poor. Rapid tumor progression, drug resistance, and high metastasis rates are common challenges with this disease, making the need for newer more effective therapies vital.
More and more, natural compounds from food are being investigated as potential anticancer agents. Garlic has been singled out for its numerous uses in preventing and treating several different ailments including diabetes and cardiovascular diseases. Large-scale studies in the past decade have also suggested a strong correlation with garlic consumption and reduced incidence with cancer. In particular, SAC in garlic has shown to be effective in reducing gynecological cancer growth. Therefore, knowing more about this substance could be helpful in treating ovarian cancer, as well as other types of similar cancers.
Epigenetics is the study of DNA modifications that affect gene activity but do not change the genetic sequence. DNA is the most characterized epigenetic mechanism and it occurs when methyl groups are added to the DNA molecule. This process is controlled at various levels in a cell and is carried out by a group of enzymes called DNA methyltransferases (DNMTs). DNMT1 maintains DNA methylation patterns, while DNMT3a and 3b mediate the establishment of new DNA methylation patterns. DNMT1, which is highly transcribed during the synthesis phase of the cell cycle, can also interact with RNAs to block gene-specific DNA Methylation. Several studies have reported that defects in DNMTs are associated with tumor transformation and progression. Plus, drugs that act as DNMTinhibitors (or demethylating agents) have been used successfully to treat certain types of cancer.
Previously, the researcher demonstrated that SAC was capable of inhibiting cell proliferation when administered to the human ovarian carcinoma cell line A2780. In this study, they measured the global DNA methylation levels of A2780 after treatment with different concentrations of SAC. For positive control, the cells were treated with a potent DNA activity of DNMT in the cells after SAC treatment, as well as the quantitative mRNA analysis of various DNMTs and tumor suppressor gene CDKN1A.agent (5-aza-dc). They also measured the
As expected, their data showed that the garlic compound reduced ovarian cancer cell growth. It also reduced global DNA methylation levels and protein expression levels of DNMT1, but not DNMT3a/DNMT3b in cells. As the authors pointed out, “DNMT1 is a maintenance methylase, which is the most important in the whole process of DNA methylation, whereas DNMT3a/DNMT3b is involved in de novo methylation.”
Furthermore, they determined that SAC affected cell cycle regulation in the A2780 cells by reactivating mRNA expression of CDKN1A, a tumor suppressor gene. This caused cell cycle arrest at the in G1/S phase, or the starting checkpoint of cell division.
“The regulation of cell cycle progression is an important system to control cancer cell proliferation.” The researchers explained. “The cell cycle is a complex process that ensures correct cell division. It is tightly regulated by arrest at the G1 or G2 checkpoints and multiple molecular pathways, including oncogenic signaling, cyclin-dependent kinases (CDKs), and their regulatory inhibitors”
Overall, the study confirms SAC’s ability to reduce ovarian cancer cell growth and indicates its epigenetic mechanism of action as DNA methylation through DNMT1. It also demonstrates DNMT1’s effect on A2780 cell cycle regulation. While further investigation is needed to identify the detailed mechanisms involved here, the data does imply that SAC has the potential to be a potent anti-cancer drug – one that might work well in combination with other chemo or radiation therapies.
Source: Xu Y et. al. (May 2018). S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1. J Ovarian Res. 11(1):39.