(NaturalNews) A gene called p53 that is known to be important in controlling cell growth and death has the ability to suppress tumors. It works as a kind of checkpoint to keep abnormal cells from growing and dividing unheeded and causing malignancies. But something --an environmental toxin, chemicals, radiation, no one knows for sure -- can mutate the gene. The result? It no longer protects the body against pre-cancerous cells, allowing them to progress into cancer. In fact, researchers have learned mutations in the p53 tumor suppressor gene play a role in about half of all human tumors.
The p53 mutation was just in the news when researchers from the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) presented results of what is believed to be the largest p53 and breast cancer study in the US. At the Annual Meeting of the American Association for Cancer Research (AACR) in Denver, Colorado, the scientists said they've found that almost 26 percent of women studied who have breast cancer were found to have mutations in this gene. What's more, the women with the gene mutation had poorer outcomes and significantly higher risk of dying from their cancer.
"The p53 gene is the guardian of the genome because it signals the cell to repair DNA damage when that occurs. If we can find genetic or environmental risk factors that lead to damage of p53 or stress on the gene, we may be able to help prevent development of breast cancer as well as other cancers," the study's lead investigator, Catalin Marian, MD, PhD, a research instructor of cancer genetics and epidemiology at the Lombardi Comprehensive Cancer Center at GUMC, said in a media statement.
Meanwhile, another research team at Lombardi Comprehensive Cancer Center at GUMC presented a remarkable discovery about how a mutant p53 gene might be "fixed". They've observed that a natural substance can restore the cancer-stopping function to p53 in a variety of human tumor cells.
Specifically, the scientists have demonstrated that phenethyl isothiocyante (PEITC), a natural compound found in cruciferous vegetables such as watercress, broccoli and cabbage, can selectively deplete mutant p53. And when this happens in human cancer cells, the researchers said there's a restoration of what they call the "wild type", i.e. normal, function of p53.
This research strongly suggests that PEITC restores the normal p53 checkpoint control pathways in mutant p53-expressing tumor cells. Bottom line: this novel finding could well mean PEITC and other natural compounds in the isothiocyante family could play important roles in both cancer prevention and the treatment of human cancers linked to mutant p53 genes.
There is a good reason why your mom has relentlessly emphasized the benefits of eating a portion of vegetables to stay healthy during your childhood and depriving yourself of a diet high in vegetables has future repercussions. Not only was she right, but there is a plethora of science to backing up this belief. Over the years, there has been an increasingly growing trend to finding natural compounds that can be employed as medical therapeutic alternatives for treating cancer patients and other diseases. The pharmaceutical industry has been substantially but slowly scaling-up research efforts and partnering up with research universities for finding natural herbal and natural alternatives to fight cancer instead of the conventional expensive and tedious large scale process of screening thousands of synthetic compounds to find a “right hit” or a one-size-fig-all solution to cancer. Also, more medical physicians are starting to develop novel protocols that combine alternative medicine in cancer patients at clinical trials who do not respond well to chemotherapy and in Alzheimer’s and Amyotrophic lateral sclerosis patients to delay dementia (ie., antioxidants). It almost seems as if mother nature has most of the answers for many human health conditions. In further support of this belief, scientists have given us valuable insight into the anti-inflammatory, antioxidant, and cholesterol-lowering benefits of resveratrol, curcumin, and green polyphenols, natural compounds that are found in red wine, curry, and green tea extracts respectively.
One particular natural compound that has generated a high level of interest in nutrition scientists, physician scientists and cell biologists is phenethyl isothiocyanate (PEITC). Along with other isothiocyanates, PEITC is a compound isolated from cruciferous vegetables that include cauliflower, broccoli, turnips, watercress, and cabbage (the chemical structure of PEITC is shown at the bottom right of the article). Numerous epidemiological and experimental studies demonstrate that PEITC possesses potent anti-oncogenic (antitumorigenic) and anti-angiogenic (the process of shrinking the blood supply of tumors). The majority of the scientific literature supports a robust effect of this compound in fighting prostate cancer. Intriguingly, unlike chemotherapy which preferably affects malignant tumor cells but normal tissue to a significant extent, PEITC only thwarts the growth of prostate cancer cells while leaving normal prostate tissue intact. Several scientific reports from different laboratories have demonstrated that PEITC not only induces a growth arrest of multiple prostate cancer cell lines, but persistent treatment with this compound induced apoptotic cell death in cancer cells. More importantly, in vivo studies in mice that have been inoculated with tumors have shown that PEITC dramatically reduced the size of tumors in a time and concentration dependent manner. However, scientists have noted that one needs to ingest copious amounts of vegetables (more than a 100 grams a month) in humans may be needed to lower the risk of prostate cancer and possibly other cancer types, underlying the need to synthesize an edible and marketable form of this compound. Thre is currently a Phase I clinical trial underway to test the beneficial effects of this compound in lung cancer. Click on the link at the end of the article below.
So, what is the mechanism by which PEITC kills prostate tumor cells?
Here are some mechanisms by which PEITC fights prostate cancer cells at multiple levels:
1) As tumor cells are highly metabolically active compared to normal cells. Thus malignant prostate cancer cells meet their high energy demand by extruding angiogenic signals that induce the formation of elaborate blood supplies. However, through undescribed mechanisms, PEITC shuts off the blood supply and delivery of nutrients by specifically stunting the sprouting and attachment of these capillaries feeding large tumors.
2) Malignant prostate cancer cells show high expression levels of the androgen receptor which is a key step for cells to achieve hormone independent growth and metastasis. PEITC specifically promotes the downregulation, endocytosis (the process by which endosomal vesicles sequester cellular material) and degradation of the androgen receptor.
3) Several laboratories have shown that PEITC shuts down the transcriptional activity of a variety of DNA genes and inactivates the synthesis of proteins that are highly induced in prostate cancer cells that are critical to achieve malignancy.
4) Surprisingly, PEITC the tumor-shrinking properties and cell death activity of this compound is due to its ability to induce autophagy (self-eating) in prostate cancer cells. One can envision that PEITC promotes “self-cannibalism” by activating certain signals in cancer cells which induce the degradation of structural elements such as microtubules (structural elements that hold the cell together like struts and beams in a building), and mediate the dismantling of other organelles such as mitochondria (energy centers of the cell) and induce proteasome mediated degradation of many proteins. A study performed by the Singh lab at the University of Pittsburgh, Hillman Cancer Research Institute has elegantly demonstrated this phenomenon elicited by PEITC in two prostate cancer model cell lines and in C. elegans models. For more information, click on the link below.
5) Finally, PEITC induces the formation of free radicals oxidants (ROS) in tumor cells but not in normal prostate cells. As a high burden of ROS has been implicated as a major contributor to aging of cells, PEITC mediates generates a high level of cytosolic and mitochondrial ROS in cancer cells. Investigators have shown that a persistent wave of ROS in cancer cells mediated by PEITC shuts down essential metabolic (ie., aconitase in mitochondria) and processing enzymes (ie., phosphatases) and “super”-activates other signaling enzymes (kinases). In other words, PEITC wreaks havoc only in cancer cell lines by altering the signaling pathways necessary for cancer cells to achieve androgen signaling independence and consequent metastasis. It is worth noting that that PEITC has other properties such as protecting the chromatin structure and underlying DNA content of cells against carcinogenic compounds by forming a protecting coat that blocks the activity of DNA intercalating agents.
Well, enough of the science and into the practical side. Currently, this compound is only available for use in research. However, As more scientific evidence identifies more weapons to add to the arsenal in the fight against cancer, it is conceivable that a conglomerate of academic institutions will focus a big portion of their research endeavors into securing NIH grants and pharmaceutical contracts to isolate, purify and produce commercially feasible mass quantities of these natural compounds for future medical use. As the FDA does not regulate the content or use of natural supplements in the market basic research, it is expected that most of these compounds do not have any teratogenic (affecting the fetus) or pleiotropic side (global) effects may pass the initial phases of clinical trials with ease.
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