Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Reexamination Certificate
2001-06-13
2002-12-24
Killos, Paul J. (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
C514S689000, C568S325000, C568S331000, C568S337000
Reexamination Certificate
active
06498195
ABSTRACT:
BACKGROUND OF THE INVENTION
Herbal products have gained popularity for their use in the treatment of diseases in humans. Although the clinical effect of most herbal products is unknown, many herbs contain derivatives with biological activity. One such herb is licorice root. Extracts of licorice root have been shown to have biological activity that includes antioxidant activity (Palagina, M. V. et al. 1999.
Ter. Arkh.
71:45-48), inhibition of melanin synthesis (Yokota, T. et al. 1998.
Pigment Cell Res.
11:355-361), inhibition of angiogenesis (Kobayashi, S. et al. 1995.
Biol. Phar,. Bull.
18:1382-1386), anti-microbial activity (Mitscher, L. A. et al. 1980.
J. Nat. Prod.
43: 259-269), anti-parasitic activity (Zhai, L. et al. 1995.
Antimicrob. Agents Chemotherap.
39:2742-2748), and anti-tumor activity (Shibata, S. 1994.
Stem Cells
12:44-52). Several compounds responsible for the various biological effects have been isolated. Examples of such compounds include glabridin (Yokota, T. et al. 1998.
Pigment Cell Res.
11:355-361), isoliquiritin (Kobayashi, S. et al. 1995.
Biol. Pharm. Bull.
18:1382-1386), glycyrrhizin (Raggi, M. A. et al. 1995.
Boll. Chim. Farm.
134:634-638), and licochalcone A, a non-hydroxylated chalcone compound (Shibata, S. 1994.
Stem Cells
12:44-52).
Recent studies with a combination of eight herbs, that included licorice root, called PC-SPES, has been shown to have potent clinical and biological activity (DiPaola, R. S. et al. 1998.
N. Engl. J. Med.
339:785-791). PC-SPES showed anti-prostate cancer activity which was attributable to phytoestrogens that produced a chemical castration. Another study demonstrated that licorice root alone was capable of decreasing circulating testosterone levels in men (Armanini, D. et al. 1999.
N. Engl. J. Med.
341:1158). Additional studies in patients have demonstrated PC-SPES to have anti-tumor activity refractory to chemical castration, thus indicating that other mechanisms may be responsible for the anti-tumorigenic activity of this licorice root-herbal combination therapy (Small, E. et al. 1999.
N. Engl. J. Med.
340(7):785-791).
PC-SPES extracts have also been shown to induce apoptosis in tumor cell lines and decreased the expression of bcl-2. Bcl-2 is a 26 kDa protein that blocks cell death by inhibiting cytochrome c release from mitochondria, a critical event in the apoptotic pathway. Overexpression of bcl-2 protects cells from death promoting stimuli, whereas lowering bcl-2 levels increases cell death and sensitivity to chemotherapy (Reed, J. C. 1997. Nature 387:773-776). Recent studies suggest that drugs which decrease bcl-2 expression, or inactivate the molecule through phosphorylation, induce apoptosis. For example, paclitaxel, docetaxol, vincristine, and vinblastine alter microtubule structure and induce apoptosis in association with bcl-2 phosphorylation (Hadlar, S. et al. 1996.
Cancer Res.
56:1253; Haldar, S. et al. 1995.
Proc. Natl. Acad. Sci. USA
92:4507-4511).
It has now been found that compounds extracted from licorice root, in particular hydroxylated chalcones, have activity consistent with induction of apoptosis and potential activity as anti-tumorigenic and anti-carcinogenic agents.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a hydroxylated chalcone compound extracted and purified from
Glycyrrhiza glabra.
In a preferred embodiment the compound comprises 1-propanone-1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl).
Another object of the present invention is to provide a method of inducing phosphorylation of bcl-2 comprising contacting cells or tissues with a hydroxylated chalcone compound.
Yet another object of the present invention is to provide a method of inducing apoptosis in cells or tissues comprising contacting cells or tissues with a hydroxylated chalcone compound.
Also included in the present invention are methods for inhibiting tumor cell growth and preventing and treating cancer via contacting tumor cells or tissues with an effective amount of a hydroxylated chalcone compound.
REFERENCES:
patent: 0998939 (2000-05-01), None
patent: 02204495 (1990-08-01), None
Yoshida et al , Two Polyphenol Glycosides and Tannins from Rosa cymosa, Jun. 1992, Phytochemistry , vol. 32, No. 4, pp. 1033-1036.*
Press Release, AACR-NCI-EORTC International Conference, New Compound Extracted From Licorice Root Shows Antitumor Activity in Acute Leukemia, Breast and Prostate Cancer (Nov. 17, 1999), available at http://www.aacr.org/1000/1100/1200ae.html (last visited on Apr. 3, 2002).
Armanini, D., et al., “Reduction of Serum Testosterone in Men by Licorice”,N. Eng. J. Med.,1999, vol. 341, p. 1158.
Combest, W. L., “Herbal pharmacy: Licorice”,U.S. Pharmacist,1998, vol. 23:4, available at http://www.uspharmacist.com/NewLook/DisplayArticle.cfm?item_num=106 (last visited on May 6, 2002).
DiPaola, R.S., et al., “Phase I clinical and pharmacological study of 13-cis-retinoic acid, interferon alfa, and paclitaxel in patients with prostate cancer and other advanced malignancies”,J. Clin. Oncol.,1999, vol. 17, pp. 2213-2218.
DiPaola, R.S., et al., “Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC-SPES) in Prostate Cancer”,N. Engl. J. Med.,1998, vol. 339, No. 12, pp. 785-791.
Edwards, M.L., et al., “Chalcones: A New Class of Antimitotic Agents”,J. Med. Chem.,1990, vol. 33, pp. 1948-1954.
Goldberg, D.M., et al., “Resveratrol Glucosides are Important Components of Commercial Wines”,Am. Jour. of Enol. Vitic.,vol. 47, No. 4, 1996, pp. 415-420.
Haldar, S., et al., “Inactivation of Bcl-2 by Phosphorylation”,Proc. Natl. Acad. Sci. USA,1995, vol. 92, pp. 4507-4511.
Haldar, S., et al., “Taxol Induces bcl-2 Phosphorylation and Death of Prostate Cancer Cells”,Cancer Res.,1996, vol. 56, pp. 1253-1255.
Hsieh, T., et al., “Regulation of androgen receptor (AR) and prostate specific antigen (PSA) expression in the androgen-responsive human prostate LNCaP cells by ethanolic extracts of the Chinese herbal preparation, PC-SPES”,Biochem. Mol. Biol. Int.,1977, vol. 42, pp. 534-544.
Iwata, S., et al., “Antitumorigenic Activities of Chalcones. I. Inhibitory Effects of Chalcone Derivatives on32Pi-Incorporation into Phospholipids of HeLa Cells Promoted by 12-O-Tetradecanoyl-phorbol 13-Acetate (TPA)”,Biol. Pharm. Bull,vol. 18, No. 12, 18(12) pp. 1710-1713 (1995).
Kobayashi, S., et al., “Inhibitory Effect of Isoliquiritin, a Compound in Licorice Root, on Angiogenesis in Vivo and Tube Formation in Vitro”,Biol. Phar. Bull.,1995, vol. 18, pp. 1382-1386.
Mitscher, L.A., et al., “Antimicrobial Agents From Higher Plants. Antimicrobial Isoflavanoids and related substances fromGlycyrrhiza GlabraL. Var.Typica”, J. Nat. Prod..1980, vol. 43, pp. 259-269.
Palagina, M.V., et al., “Pulmonary Metabolism and Its Correction in Radiotherapy of Thoracic Tumors”,Ter. Arkh.,1999, vol. 71, pp. 45-48. Foreign language—English Abstract.
Rafi, M.M., et al., “Modulation of bcl-2 and Cytotoxicity of Licochalcone-A, a Novel Estrogenic Flavonoid”,Proceedings of the 1999 AACR-NCI-EORTC International Conference,Abstract #263; published as a supplement toClinical Cancer Research,1999, vol. 5, ISSN. 1078-0432.
Rafi, M.M., et al., “Modulation of bcl-2 and Cytotoxicity by Licochalcone-A, a Novel Estrogenic Flavonoid”,Anticancer Res.,2000, vol. 20, No. 4, pp. 2653-2658.
Rafi, M.M., et al., “Novel Derivative from the Licorice Induces Apoptosis and Phosphorylates Bcl-2”, 2001, Proceedings from the American Association of Cancer Research, vol. 42, Annual Meeting in New Orleans, LA, Mar. 24-28 (2001), Abstract #1009.
Rafi, M.M., et al., “Modulation of bcl-2 by flavonoids isolated fromglycyrrhiza inflata”,2000, Proceedings of the American Association for Cancer Research, Annual Meeting, Mar., (2000), Abstract #4692.
Rafi, M.M., et al., “Licochalcone-A: A novel phytoestrogen with antitumor activity in Breast and prostate tumor cell lines”, 1999, Proceedings from the American Society of Clinical Oncology, Annual Meeting in Atlanta, GA, May 15-18 (1999), vol. 18 Abstract #712.
Raggi, M.A., et al
DiPaola Robert S.
Ghai Geetha
Ho Chi-Tang
Rafi Mohamed M.
Rosen Robert T.
Killos Paul J.
Oh Taylor V
ReedSmith LLP
Rutgers The State University of New Jersey
LandOfFree
Use of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2940317