Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Milk or colostrum
Patent
1995-05-08
1999-03-30
Witz, Jean C.
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Milk or colostrum
514 2, 514 21, 514251, 514276, 514885, 530365, 530833, 426 72, A61K 3520
Patent
active
058885528
DESCRIPTION:
BRIEF SUMMARY
SUMMARY OF THE INVENTION
The present invention is based on the surprising discovery that undenatured whey protein concentrate has an enhanced immunological effect. More specifically, this invention relates to the effect of the oral administration of undenatured whey protein concentrate (WPC) on host resistance to the development of chemically induced cancer and also the effect of such oral administration on the inhibition of cancer.
In U.S. application Ser. No. 298,971 and Ser. No. 417,246, and also in Bounous et al "Dietary Whey Protein Inhibits the Development of Dimethyl-hydrazine induced Malignancy" (1) we described experiments showing that continuous feeding of WPC in the diet inhibits the development (number and size of tumours) in the colon of a mouse over a period of 24 weeks of dimethylhydrazine (DMH) treatment. This anti-tumour effect could be caused by increased resistance of target cells to the carcinogen and/or a direct inhibitory effect of WPC on the cancer cells. A subsequent series of experiments (2) where animals were fed Purina diet for the first 20 weeks of DMH and then switched to WPC diet for the remaining 8 weeks of DMH treatment, suggested some inhibitory effect of WPC feeding on cancer cells.
Most recently (3) a group of French scientists confirmed in vitro a direct inhibitory effect of WPC on human cancer cells. Indeed similar studies in vitro with human breast cancer cells have shown that bovine serum albumin (BSA) is the factor exerting inhibition of cancer cell replication (4).
We have also shown that this activity of WPC is specifically dependent upon the glutamylcysteine groups (substrate for GSH synthesis) present in the BSA fraction of WPC (U.S. Ser. No. 563,794). Interestingly, the introduction of the cysteine delivery system ozothiazolidine-4-carboxylate (OTZ) (ozothiazolidine-4-carboxylate), while enhancing glutathione (GSH) levels in normal cells, was found to result in feedback inhibition of the GSH cycle in human tumour cells (5). This differential effect of OTZ was recently confirmed in vivo (6). The previously described direct inhibitory effect of WPC (3) and more specifically of BSA (4) could be explained therefore by the release during incubation of a potent cysteine delivery system such as glutamylcysteine.
We have therefore reached the following conclusions:
1) BSA is the protein fraction of WPC that we found to be primarily responsible for the GSH promoting activity of WPC. This activity which we believe to be the basis for the immuno enhancing and anticarcinogen effect of WPC, is specifically dependent upon the glutamylcysteine groups (substrate for GSH synthesis) present in the BSA fraction of WPC.
2) The molecular weight of BSA is 66,267 hence quite different from the KW of the anti-cancer factor patented by Villadsen (MW 500-20,000). (7).
3) Our earlier findings (1,2) could be explained as follows: During DMH treatment, WPC feeding, by increasing cellular GSH, protects the target cells against the effects of the carcinogen. In addition, increased availability of substrate for GSH synthesis could inhibit replication of formed cancer cells.
4) We have now established the importance of a high level of serum albumin (BSA) in the WPC in providing a substrate for GSH synthesis. We can conclude that dietary whey protein concentrate in undenatured form and containing .gtoreq.10% BSA exerts an anti-tumour effect.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates the liver glutathione content in male mice C57BL/6NIA fed undenatured whey protein (U-Lacp), denatured whey protein (D-Lacp), casein, egg white protein or Purina diet-fed counterparts at age 10 weeks, 27, 20 and 21 months.
FIG. 2 illustrates the heart glutathione content of male mice C57BL/6NIA fed undenatured whey protein (U-Lacp), denatured whey protein (D-Lacp), casein, egg white protein or Purina diet-fed counterparts at age 10 weeks, 17, 20 and 21 months.
FIG. 3 illustrates the effect of various sources of whey protein concentrate and casein (20 g/100 g. diet) on spleen PFC response to 5.times.10.
REFERENCES:
patent: 4784685 (1988-11-01), Meister
Anderson, M.E., "Tissue glutathione", C.R.C. Handbook of Methods for Oxygen Radical Research, pp. 317-329 (1985) (Exhibit 1).
Lauterburg, B.H. et al., "Therapeutic doses of acetaminophen stimulate the turnover of cysteine and glutathione in man", J. Hepatol., vol. 4, pp. 206-211 (1987) (Exhibit 2).
Lewis, A.D. et al., Proc. Natl. Acad. Sci., vol. 85, pp. 8511-8515 (1988) (Exhibit 3).
Russo, A. et al., "Selective modulation of glutathione levels in human normal versus tumor cells and subsequent differential response to chemotherapy drugs", Cancer Res., vol. 46, pp. 2865-2848 (1985) (Exhibit 4).
Walstra, P.J., "Dairy Chemistry and Physics", Wiley J. Nitork, (ed.), p. 106 (1984) (Exhibit 5).
Williamson, J.M. et al., "Intracellular cysteine delivery system that protects against toxicity by promoting GSH synthesis", Proc. Natl. Acad. Sci. U.S.A., vol. 79, pp. 6246-6249 (1982) (Exhibit 6).
Bounous, G., et al., "Dietary Whey Protein Inhibits the Development of Dimethylhydrazine Induced Malignacy." Clin. Invest. Med., (1980) vol. 11, pp. 231-217.
Papenburg, R., et al., "Dietary Milk Proteins Inhibit The Development of Dimethylhydrazine-Induced Malignacy." Tumor Biology, (1990) vol. 11, pp. 129-136.
Baruchel, S., et al., (1992) AACR Abstract, "Different Effects of OTZ on Organ GSH Levels in Rate Bearing Tumors".
John, A.M, et al., "Amino Acid Requirements of the Growing Mouse." J. Nutr., (1976) vol. 106, pp. 1361-1367.
Hoag, W.G., et al., "Nutrition" In: Biology of the Laboratory Mouse, E.L. Green, (ed.), (McGraw-Hill, New York: 1966) pp. 39-43.
Cunnigham, A., et al., "Further Improvements in the Plaque Technique for Detecting Single Antibody Forming Cells." J. Immun., (1968) vol. 14, pp. 559-600.
Anderson, M.E., "Tissue Clutathione" In: Handbook of Methods for Oxygen Radical Research. (C.R.C. Press, Boca Raton: 1988) pp. 317-329.
Glatt, H., et al., "Mutagenicty of Glutathione and Cysteine in the Ames Test." Science, (1983) vol. 220, pp. 961-962.
Taylor, Y.C., et al., "Elevation of Intracellular Glutathione Levels Following Depletion and its Relationship to Protection Against Radiation and Alkylating Agents." Pharmacol. Ther., (1988) vol. 39, pp. 293-299.
White, C.W., et al., "Hypoxia Increases Glutathione Redox Cycle and Protects Rat Lungs Against Oxidates." J. Appl. Physiol., (1988) vol. 65, pp. 2607-2616.
Anderson, M.E., et al., "Transport and Direct Utilization of Gamma-Glutamylcyst(e)ine for glutathione Sythesis." Proc. Natl. Acad. Sci. U.S.A., (1983) vol. 80, pages 707-711.
Richie, J.P., et al., "Correction of a Glutathione Deficiency in the Aging Mosquito Increses its Longevity." Proc. Soc. Exp. Biol. Med., (1987) vol. 184, pp. 113-117.
Fernandez-Checa, J.C., et al., "Effects of Chronic Ethanol Feeding on Rat Hepatocyte Glutathione." J. Clin. Invest., (1989) vol. 83, pp. 1247-1252.
Meister, A., et al., "Glutathione." Ann. Rev. Bloch., (1983) vol. 52, pp. 711-760.
Hamilton, T.C., et al., "Augmentation of Adriamycin, Melphalan and Cisplastin Cytoxicity in Drug Resistant and Sensitive Human Ovarian Cancer Cell Lines by BSO Mediated GSH Depletion." Biochem. Pharm., (1985) vol. 34, pp. 2583-2586.
Suzukake, K., et al., "Dechlorination of L-Phenylalanine Mustard by Sensitive and Resistant Tumor Cells and its Relationship to Intracellular Glutathione Content." Biochem. Pharm., (1983) vol. 32, pp. 165-171.
Enker, W.E., et al., "Experimental Carcinogenesis of The Colon Induced by 1,2-Dimethylhydrazine-di HC1: Value as a Model of Human Disease." J. Surg. Res., (1976) vol. 21, pp. 291-299.
Corbett, T.H., et al., "Evaluation of a Single Agent and Combination of Chemotherapeutic Agents in Mouse Colon Carcinogenesis." Cancer, (1977) vol. 40, pp. 2650-2580.
Bounous, G., et al., "The Biological Activity of Undenatured Dietary Whey Proteins: Role of Glutathione." Clin. Inves. Med., (1991) vol. 14, pp. 269-309.
Bounous, G., et al., "Immunoenhancing Property of Dietary Whey Protein in Mice: Role of Glutathione." Clin. Invest. Me
Bounous Gustavo
Gold Phil
Immunotec Research Corporation Ltd.
White John P.
Witz Jean C.
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