The Superhero of all Vegetables: Broccoli

                  Broccolis, the vegetable that most mothers have to tell their children to finish at least once in their life may contain potential superpowers involved in the suppression of tumors or cancerous cells. Researchers have recently discovered that eating cruciferous vegetables or plants of the cabbage family such as broccoli, cauliflower and watercress helps prevent the cancerous cells in your body from being switched on. According to current research and data, epigenetics plays an important role in suppressing the harmful carcinogenic cells in an individual’s body. Epigenetics refer to the study of how heritable gene expressions derived from environmental factors and do not involve the alterations of the underlying primary DNA sequence. This branch of science plays an important role in the study of diseases and health issues as it explains how an individual’s diet, habits and other environmental factors have the ability to alter or switch “on” and “off” gene expressions.

Sulforaphane (SFN), a chemical compound found in cruciferous vegetables is the factor responsible in preventing cancer through the complex process of epigenetics. Researchers of Clinical Epigenetics (Hsu et al. 2011) conducted a research titled “Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells” in an attempt to discover how the chemical components of cruciferous vegetables epigenetically alter our gene expressions to inhibit cancer.

                   Scientists have recently discovered that the chemical compound sulforaphane alters gene expression through an epigenetic process by acting as a dietary histone deacetylases (HDAC) inhibitor, a family of enzymes that interferes with the normal function of genes that suppress tumors. This chemical compound has been shown to do many significant tasks that helps regulate gene expression in breast cancer, gastric cancer, colon cancer, etc. The aim of this research is to evaluate the effects of SFN on epigenetic regulation of cyclin D2 in prostate cancer cells. Firstly, let’s clarify some complicated terminologies. Cyclin D2 is a family of protein that is known to regulate the progression of cell cycle, mainly in the G1 and S phase of the cycle. If under any circumstances the protein malfunctions, it could induce the abnormal growth of bodily tissues. According to the research, Cyclin D2 has been identified in several cancer cases as a proto-oncogene. Any over-expression or under expression of the protein can bring about several types of cancer. DNA-methylation is “a normal process of turning off genes, and it helps control what DNA material gets read as part of genetic communication within cells”. In addition, the results of the experiment indicate that SFN is also capable of suppressing DNA methyltransferases (DNMTs), a type of enzyme that controls the regulation of the gene expressions of cancerous cells.  

                  In order to conduct the experiment, researchers utilized cells that were cultured and treated in laboratories. The three types of cells used include benign prostate hyperplasia (BPH-1) cells, androgen dependent prostate cancer epithelial cells (LnCap) and androgen-independent prostate cancer epithelial cells (PC3). Benign prostate hyperplasia cells refers to the enlargement of the prostate gland common in elderly men, while androgen prostate cancer epithelial cells are cells found along the body’s cavities that stimulates the development and maintenance of male characteristics.  After being treated with various chemicals, the DNA sequence of each cell was amplified using quantitative polymerase chain reaction. This type of PCR enables both detection and quantification of DNA sequence. A series of diluted copies of the DNA sequence served as the standard or benchmark for quantification. Next, researchers used what is known as the western blot analysis, which is an analytical technique used to detect specific proteins in a given sample of tissue.

After various treatments were applied to all cell types, data points were collected and statistical difference between SFN treated cells and other treatments were determined and found that the difference of results were statistically significant with a P value of less than 0.05. During the experiment, the effects of SFN on the expressions of DNMTs (DNMT1, DNMT3a and DNMT3b) were tested BPH-1, LnCap and PC3 prostate cancer cells as mentioned before. Cells were treated with different amounts of sulforaphane (15 um and 30 um) and were tested for the DNMTs after 48 hours. Results of the experiment as presented in the diagram above show that both doses of sulforaphane significantly decreased DNMT1 and 3b mRNA expression. In LnCap cells, SFN also decreased mRNA expressions of DNMT1 and 3b and DNMT1 protein expression. Moreover, the experiment showed that sulforaphane decreased Cyclin D2 promoter methylation.

As previously mentioned, DNA methylation is the process of regulating gene expression by turning “on” and “off” specific genes. A tightly regulated balance exists in normal cells among these processes, but disruption of this balance contributes to the development of cancer. Basically, what it comes down to is that ingesting food products with SFN can prevent this malfunctioning of normal cells as recent studies have shown that SFN contain chemo-preventative properties such as HDAC and DMNT inhibitors. According to Emily Ho, an associate professor in the Linus Pauling, “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's where some of these critical nutrients are involved. They help restore the balance." Findings of this experiment provide promising insights into how sulforaphane (SFN) is capable of epigenetically altering gene expression to prevent prostate cancer.

Credits:

1. "Eat Your Broccoli: Another Mechanism Discovered by Which Sulforaphane Prevents Cancer." ScienceDaily. ScienceDaily, 28 Feb. 2012. Web. 30 Apr. 2012. <http://www.sciencedaily.com/releases/2012/02/120228140555.htm>.
2. "Epigenetics: DNA Isn’t Everything." ScienceDaily. ScienceDaily, 12 Apr. 2009. Web. 30 Apr. 2012. <http://www.sciencedaily.com/releases/2009/04/090412081315.htm>.
3. Hsu et al.: Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells. Clinical Epigenetics 2011 3:3/ 
4. "Broccoli Fights Cancer by Clearing Bad Tumor Suppressors: Scientific American Podcast." Science News, Articles and Information. Web. 30 Apr. 2012. <http://www.scientificamerican.com/podcast/episode.cfm?id=broccoli-fights-cancer-by-clearing-11-01-27>.
5. "How Broccoli Fights Cancer." Discovery News. Web. 30 Apr. 2012. <http://news.discovery.com/human/how-broccoli-fights-cancer-110310.html>.
6. "Breasts, Broccoli and Cancer." Alternative & Natural Cancer Treatments-Cancer Treatment Alternatives Options-. Web. 30 Apr. 2012. <http://www.anoasisofhealing.com/breasts-broccoli-and-cancer>.

                 

                 

                 

                 

                 

                  

The Letters that Code for Our LIves

The Alphabet of Life by Marissa Cevallos, an article in the ScienceNews magazine, sets off to search for clues to the origin of genetic codes, or the codes that govern our lives. Surprisingly, only four letters make up the overall sequence of the genetic code. According to the research, these letters (A, C, G and T) also known as nucleotides "combine to spell out the more than five dozen three-letter words that encrypt the information needed to make all the cells int he human body, and any other body as well." The sequence of nucleotides  are responsible for coding the "instructions for making proteins." Unfortunately, the quest to discover how life's code came to be becomes a difficult one when there is no way to replicate life's earliest days, so scientists are stuck with only one version (us humans) to study in order to decipher the possible origin of the fundamental codes. The author of the article interestingly compares sets of codons to the concept of synonyms. She mentions this in the article because often times, three or four codons will code for the same amino acid. This feature was thought to have been developed in order to protect cells from making errors: for example, if RNA's CGA mutates to CGU, the cell will still code for the same amino acid despite the mistake it has made earlier. Tsvi Tlusty of Weizman Institute of Science in Rehovot, Isarael believes that the genetic code does its job so well because it has adapted under evolutionary pressure, much like Darwin's theory of natural selection. According to Tlusty, the three possible pressure that shaped the current genetic code includes the " inability of typos to be disastrous, the language (codes) must spell words with diverse meanings and the language shouldn't take a lot of resources to write."


E. Koonin noticed that changing the last letter in a set of triplet codons does not drastically change the overall amino acid. Therefore, he concluded that "early genetic code relied on only the first two of its three letters." Through experimentation, Koonin's team found that minimizing errors was the thing that caused the genetic code's development - "when having more than 16 amino acids was advantageous, the code started to use the third letter."


In order to determine which amino acids came first, we have to turn over to the chemistry side of the puzzle. In his famous spark tube experiment, Stanley Miller created a handful of life's amino acids by electrically zapping together hydrogen, water, methane and ammonia gases. Surprisingly, five amino acids that were created in this experiment were found within meteorites - glycine, alanine, aspartic acid, glutamic acid and valine. Each of the codons that code of these amino acids starts with a letter G, suggesting that G may have been the first letter to code for an amino acid. Another scientists believed that the first amino acids were the ones with a natural chemical attraction to RNA.


In another case the researchers at the Georgia Institute of Technology in Atlanta are trying to approach the problem by going back into time. Biochemist Loren Williams has turn to look at ribosomes, the factory which is essential in generating proteins. Williams has found that some of the oldest RNAs are situated inside the ribosome due to its densely connected nature with other RNAs. According to his findings, Williams argues that the oldest protein situated inside the protein means that these amino acids may have been first to join the code. In another approach, aerobiologist Eric Gaucher is currently comparing individual protein in different living organisms to try to estimate a likely protein ancestor.

Despite the exhaustive amount of  research that have been done concerning this area of interest, genetic code still holds many, puzzling mysteries and secrets for biologists all around the globe, proving that a task like this is not an all easy to accomplish. In my opinion, the quest to search for the origins of the genetic code holds a lot of importance in understanding how proteins, the essential part of all living organisms, function at a deeper level. Studying the past may lead scientists to discover amazing things about protein for future generations. Sometimes it's necessary to take one step back in order to be able to move three steps forward.