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Medical Reports

The p53gene

The p53 gene exists in all human cells and might be considered one of the most important human genes. It controls an extremely important cellular process known asapoptosis.

Apoptosis can simply be described as programmed cell death. The reason we’re not all 20 feet tall and weigh a thousand pounds is that cells have a limited lifespan. When this lifespan has been fulfilled, the p53 initiates a cascade of processes that

result in controlled cell death and the recycling of usable cellular material. The p53 gene can also be described as the protector of the genome (our DNA) because if harmful mutations occur (those that could result in cancer) it may also initiate the mutation damages the p53 gene so that it cannot do its job, cancer can result. In fact, it is now believed that as many as 50% or more of human cancers result from damage to the p53 gene.

Life Sci 2002 March 1st

 

 Mar 1;70(15):1821-39 Related Articles, Books, LinkOut

Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants.

Narayanan BA, Narayanan NK, Stoner GD, Bullock BP.

Microarray Systems Laboratory, American Health Foundation, Valhalla, NY 10595, USA. bhagavat@mindspring.com

Dietary phenolic compounds are known to elicite vital cellular responses such as cell cycle arrest, apoptosis and differentiation by activating a cascade of molecular events. As there is an increasing interest to improve the efficacy of these compounds for use as potential chemopreventive agents, we wanted to understand the impact of phenolic compounds on target genes in prostate cancer. In this study we used human cDNA microarrays with 2400 clones consisting of 17 prosite motifs to characterize alterations in gene expression pattern in response to the phenolic antioxidants ellagic acid (EA) and resveratrol (RE). Over a 48-hr exposure of androgen - sensitive LNCaP cells to EA and RE, a total of 593 and 555 genes respectively, showed more than a two fold difference in expression. A distinct set of genes in both EA-and RE-treated cells may represent the signature profile of phenolic antioxidant-induced gene expression in LNCaP cells. Although extensive similarity was found between effects of EA - and RE - responsive genes in prostate cancer cells, out of 246 genes with overlapping responses, 25 genes showed an opposite effect. Quantitative RT-PCR was used to verify and validate the differential expression of selected genes identified from cDNA microarrays. In-depth analysis of the data from this study provided insight into the alterations in the p53 - responsive genes, p300, Apaf-1, NF-kBp50 and p65 and PPAR families of genes, suggesting the activation of multiple signaling pathways that leads to growth inhibition of LNCaP cells. This is a first study to look for changes in a large number of human genes in response to dietary compounds. 

History of the Research

Influential scientists such as Dr. Daniel Nixon of the Hollings Cancer Institute (Medical University of south Carolina, USA) have been working with certain micro-nutrients and their impact on human health. Dr. Nixon’s most recent work has been with raspberries and specifically the micronutrient ellagic acid contained in the pulp and seeds. His work with tissue cultures has shown that cancer cells (of many types) exposed to ellagic acid levels corresponding to specific amounts of eating fresh raspberries underwent a natural cell death.

This is incredibly important news, because the amount of raspberries needed to develop this level of ellagic acid was only one cup!

Dr. Nixon has also shown that human cervical cells infected with human papilloma virus (HPV, warts) are also killed by the same concentration of ellagic acid. This is important because human papilloma viruses are considered to be the main cause of cervical cancer.

Other scientist have found positive responses using ellagic acid in researching many other conditions and disease:

Periodontal disease
Protection of the liver from toxic injury
Faster would healing
Radiation induced chromosomal damage
Slowing the spread of the HIV virus in the human body
Slowing the degenerative process of aging
Prevention of neural tube birth defects Neurodegenerative diseases
Diabetic retinopathy

How Does the p53 Work?

The p53 gene exists in all human cells and might be considered one of the most important human genes. It controls an extremely important cellular process known asapoptosis.

Apoptosis can simply be described as programmed cell death. The reason we’re not all 20 feet tall and weigh a thousand pounds is that cells have a limited lifespan. When this lifespan has been fulfilled, the p53 initiates a cascade of processes that

result in controlled cell death and the recycling of usable cellular material. The p53 gene can also be described as the protector of the genome (our DNA) because if harmful mutations occur (those that could result in cancer) it may also initiate the mutation damages the p53 gene so that it cannot do its job, cancer can result. In fact, it is now believed that as many as 50% or more of human cancers result from damage to the p53 gene.

Anticancer Res 2001 Nov-Dec

Strong antioxidant activity of ellagic acid in mammalian cells invitro revealed by the comet assay. Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R. Dipartimento di Biologia, Universita degli Studi Roma TRE, Italy.Oxidative stress due to oxygen and various radical species is associatedwith the induction of DNA single- and double-strand breaks and is consideredto be a first step in several human degenerative diseases, cancer andageing. Naturally occurring antioxidants are being extensively analysed fortheir ability to protect DNA against such injury. We studied three naturallyoccuring compounds,Ascorbic Acid, Melatonin and Ellagic acid, for theirability to modulate DNA damage produced by two strong radical oxygeninducers (H2O2 and Bleomycin) in cultured CHO cells. The alkaline Cometassay was used to measure DNA damage and a cytofluorimetric analysis wasperformed to reveal the intracellular oxidative species. The data showed amarked reduction of H2O2- and Bleomycin-induced DNA damage exerted byEllagic Acid. On the contrary Ascorbic acid and Melatonin appeared to inducea slight increase in DNA damage per se. In combined treatments, they causeda slight reduction of H2O2-induced damage, but they did not efficientlymodulate the Bleomycin-induced one. The Dichlorofluorescein diacetate(DCFH-DA)cytofluorimetric test confirmed the strong scavenging actionexerted by Ellagic Acid.

Raspberries in the News Interest Article

Greetings Folks,

Someone kindly shared the following information with me that was in the June 04, 2002 issue of ‘Woman’s Day’ magazine, it had this to say: (page 18 --Theme: Brand-New Miracle Weight-Loss Breakthroughs!) Article title: The powerful metabolism-booster discovered in raspberries

This month, Japanese dieters will be the first to try what could soon become the world’s most delicious diet pill. Made from the compound that gives raspberries their fragrance, the chewable tablets were proven during trials to have three times more metabolism-boosting power than other popular supplements. In fact, the average test subject lost 2.2 pounds in a week without making any other lifestyle changes!

So when will the pill be widely available? It could be months or even years before they make it to your local drugstore. But there is a simple alternative, say researchers. Eat raspberries! To get enough of the fruit’s miracle ingredient, called ketones, you’ll need to incorporate two or more cups of raspberries into your daily menus.

“It worked for me!”

When Susan Gombert, R.N., first invented a raspberry diet for herself, she was pretty sure it’d help her shed a few pounds fast. “I had learned that raspberries are one of the highest fiber fruits—and fiber helps reduce both hunger and the number of calories our bodies can absorb,” says the Port Washington, New York, mom of four. “They’re incredibly low in calories, even lower than most other fruits. Plus, I’ve found that raspberries can actually take away my cravings for chocolate!”

So Susan began aiming to eat a pint of raspberries a day, adding them to cereal or just eating them straight from the container. “I found I could lose at least two pounds in a week this way, without making any other changes,” she reports. “Now if I notice my jeans getting snug, I don’t make a big deal about it, I just eat raspberries.”

This might be your weight-loss miracle if. . . you’ve always wanted to reap the benefits of diet supplements –reduced hunger, fewer cravings, reduced calorie absorption and increased fat-burning power—but have felt uneasy about taking pills. “Raspberries are all natural and truly slimming.” promises Joy Bauer, R.D., author of ‘The 90/10 Weight Loss Plan.’

6/18/02 Typed from article in Woman’s Day Magazine, June 04, 2002 Issue, Page 18

Basic Mechanisms of the Disease Process

 We live in a remarkably polluted environment. These pollutants can combine with the oxygen species known as free radicals. These free radicals seek to neutralize their imbalanced electrical charge by attacking weaker molecules-and DNA is a great target. Chromosomes have their own defensive system to deal with certain levels of free radical attack, but the burdens of modern life can overwhelm these defenses. 

Viral Intetrass, HIV Infection & Ellagic Acid

 Recent studies have shown that ellagic acid has some activity in virto (the lab) against HIV (the virus that causes AIDS). This activity is explained on the basis of its anti-integrase activity. Integrates are enzymes necessary for virues to insert their DNA into the infected cells and then use the cell machinery to reproduce itself. The ellagic acid binds to a segment of the viral integrase, rendering it incapable of carrying out its function. It thus has anti HIV capability.

Nurt Cancer, 2008 Mar-Apr, 60 (2).227.34 Links

 Dietary berries and ellagic acid diminish estrogen-mediated mammary  tumorigenesis in ACI rats. Aiyer HS, Srinivasan C, Gupta RC. Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202,  USA.
Estrogen acts as a complete mammary carcinogen in ACI rats. Prevention  studies in this model allowed us to identify agents that are effective against 
estrogen-induced mammary carcinogenesis. In this study, we investigated efficacy  of dietary berries and ellagic acid to reduce estrogen-mediated mammary  tumorigenesis. Female ACI rats (8-9 wk) were fed either AIN-93M diet (n = 25) or  diet supplemented with either powdered blueberry (n = 19) and black raspberry  (n = 19) at 2.5% wt/wt each or ellagic acid (n = 22) at 400 ppm. Animals received implants of 17beta-estradiol 2 wk later, were palpated periodically for mammary tumors, and were euthanized after 24 wk. No differences were found  in tumor incidence at 24 wk; however, tumor volume and multiplicity were  reduced significantly after intervention. Compared with the control group (average tumor volume = 685 +/- 240 mm3 and tumor multiplicity = 8.0 +/- 1.3), ellagic acid reduced the tumor volume by 75% (P < 0.005) and tumor multiplicity by 44% (P < 0.05). Black raspberry followed closely, with tumor volume diminished by > 69% (P < 0.005) and tumor multiplicity by 37% (P = 0.07).
Blueberry showed a reduction (40%) only in tumor volume. This is the first report showing the significant efficacy of both ellagic acid and berries in the prevention of solely estrogen-induced mammary tumors. 

Oxidatice Stress & the Degenerative Effects of Aging

 If an organism’s ability to generate reactive oxygen species (free radicals) is not balanced by equal amounts of anti-oxidant potential that organism is said to suffer oxidative stress. It is thought that this oxidative stress and the resultant free-radical damage strongly contributes to the degenerative effects of aging, such as arthritis, cataracts, decreased vision, and cancer itself. 

Ellagic Acid, the Phase II Enzyme System & DNA Adducts

Ellagic acid has other beneficial effects on human health that take advantage of its separate but important anti-oxidant potential. Again, to understand this important function we must have a basic understanding of what anti-oxidants are and how they protect us.

The very act of breathing in oxygen creates within living systems very reactive and damaging molecules which are combinations of oxygen and hydrogen. These reactive species are catalyzed (produced) by certain metals that are located near our DNA molecules. These reactive species will seek to neutralize their imbalanced electrical by attempting to combine with nearby healthy molecules creating damage. Since the relative species are in close proximity to DNA molecules our genes can become a likely target resulting in DNA damage (mutations). It is known that ellagic acid can form adducts (gentle wrapping of our DNA molecules) with our genes and itself become a target for the reactive species and thus protecting the DNA. This protection of necessary molecules could be termed anti-oxidant potential.

When we speak of anti-oxidants we must also mention the phase II enzyme system and its function. Within our cells and particularly the liver there are groups of enzymes that may collectively be characterized as the phase I and the phase II system.

The Antibiotic Anti DNA Gyrase Activity & Capabilities of Ellagic

 Other laboratory studies have shown the ellagic acid can act to prevent super coiling of certain bacterial DNA. This super coiling results in the twisted double helix structure of DNA of which most people are familiar. If this twisted double helix cannot develop bacteria will cease to function. It is known that the twisting is produced by enzymes known as gyrases. The ellagic acid molecule is known to bind to the gyrase enzymes, preventing the twisting of the DNA molecule. 

The Raspberry Revolution -The Miracle Berry That Helps Fight Cancer

 "The Miracle Berry that helps fight cancer"

With contributions by Susan Thorpe, Ph.D.

There has occurred over the last few decades a revolution in the way we view our healthcare. No longer are people passively waiting for the doctor to “fix them”, but are taking an active role in maintaining their own health. “Eating healthy” used to mean simply not eating “bad” foods. Now we are learning more about foods: they can be more than simply fuel. Some chemicals in certain foods are being given credit as powerful agents that can prevent or cure diseases: Nutritional Pharmaceuticals or Nutraceutical. Simply put, if a person’s family history or lifestyle indicates a high potential disease, to minimize the effects of this disease, or to improve the healing process in conjunction with other traditional treatments.

So what is a nutraceutical?

A nutraceutical is a food substance or part of a food that provides medical or health benefits, including the prevention or treatment of disease. They are naturally occurring compounds of found in plants, alga's, microbials, and other biological sources that support specific bodily health functions. Nutraceuticals are thought to have their greatest influence in preventative medicine (I.e. cancer) and for the treatment of chronic diseases.

But before we can explain to you how these nutraceuticals are able to prevent cancer we must first know what cancer is. What follows is a history of the research, a discussion of the basic mechanisms of this disease process, and how nutritional factors can protect us.

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