Promising Cancer Research

by Admin on May 13, 2013


Ellagic Acid Research

Over the last 30 years there has been a great deal of information accumulated in the literature concerning the carcinogenic process. It has been established that disruption of the delicate balance between cell growth and programmed cell death (apoptosis) in favor of the former by inhibiting or slowing down the latter, results in tumor formation. There are two apoptotic pathways: a) the so called “stress pathway” or intrinsic pathway which is initiated by profound damage to the DNA by either chemotherapy and/or radiation; and b) the extrinsic pathway which is initiated by binding of specific cytokines released by cells to their so called “death receptors” expressed on cancer cells also following heavy damage of the DNA. The binding of cytokines to their death receptors exposed on the cancer cells will result in programmed cell death. Both apoptotic pathways meet at the caspase level. Caspases are enzymes that initiate and perform apoptosis. There are several big differences between apoptosis in cancer cells and normal cells. A normal cell has a very efficient base excision repair system and any damage to DNA is immediately and efficiently repaired. By definition, a normal cell with irreparable DNA/mutations must undergo apoptosis because of activation of p53 through the intrinsic pathway. Some cells with mutations do not die because they are resistant to apoptosis. These cells become cancer cells. Most of the time, the apoptotic process is inhibited from inside the cell by the inhibitors of apoptosis (IAPs). Normal cells do not have any inhibitors of apoptosis.

Casein kinase 2 (CK2) is a kinase that is important for cell proliferation and is over-expressed in all types of cancer studied thus far. There is an overwhelming amount of data gathered in the literature demonstrating that CK2 is over-expressed in tumor cells and is involved in the apoptosis-resistance phenotype of most malignant cells. The emerging hypothesis is that high concentrations of CK2 generate a cellular environment that is favorable to both the establishment and the development of the tumor phenotype. CK2 is localized in the cytoplasm of normal cells. However, in cancer cells, CK2 is also localized in the nucleus and is deregulated, being elevated 3- to 7- fold. The up-regulation and hyperactivity of CK2 in the nucleus has an anti-apoptotic effect and is correlated with aggressive tumor behavior in a multitude of different cancer cell types examined.

Ellagic acid (abundant in pomegranate and red and black raspberries) has been identified as a very potent CK2 inhibitor. The Ki of ellagic acid for CK2 is 20 nM. It has been shown that ellagic acid alone will kill several cancer cell lines through the apoptotic process. Ellagic acid is found naturally in pomegranate and raspberries and is transformed into urolithins that remains in plasma for a longer time. There are a multitude of publications demonstrating that casein kinase 2 maintains a high concentration of IAPs inside the cancer cells. In contrast, a simple inhibitor of casein kinase 2 will induce cell death through apoptosis in all cancer cells studied thus far, without affecting any other normal cell/tissue.

We determined the content of ellagic acid and derivatives in Meeker Red Raspberry powder and in the Black Raspberry Seed powder. Ellagic acid and its derivatives from the two samples were first separated by high pressure liquid chromatography (HPLC) prior or after acid hydrolysis. It is noteworthy that acid hydrolysis of each powder releases several urolithins which were identified according to their molecular mass. The separated components were identified by mass spectrometry. Each peak was quantified and compared to a standard made of serial dilutions of purified ellagic acid. Under the conditions employed we have determined that the Meeker Red raspberry contains 0.128 ± 0.005 mg of pure ellagic acid per gram of powder, while the Black Raspberry Seed contains 0.38 ± 0.024 mg of pure ellagic acid per gram of powder.

Following acid hydrolysis (2 hrs in 2N HCl, 50% MeOH at 95°C) we have determined that the Meeker Red raspberry powder contains 23.7 ± 8.32 mg of ellagic acid and derivatives per gram of powder while the Black Raspberry Seed powder contains 41 ± 2.1 mg of ellagic acid and derivatives per gram of powder. The powders are usually dispensed orally with a scoop, provided within the container. The scoop contains 19 grams of powder. Under these conditions, two scoops of Meeker Red raspberry powder or of Black Raspberry Seed powder taken orally (and as a consequence subjected to acid hydrolysis in the stomach), will release approximately 1.1 gr and 1.6 gr respectively of ellagic acid and derivatives. In order to maintain a constant amount of ellagic acid and urolithins in the blood stream this procedure should be repeated daily or at least every other day.

Source: Research Cleveland State University

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