Claims
- 1. A method of treating a cancer in a subject, comprising administering an effective amount of a beta-lactone to the subject, thereby treating the cancer in the subject.
- 2. The method of claim 1, wherein the cancer comprises cells that express fatty acid synthase.
- 3. The method of claim 1, wherein the cancer is a leukemia, a lymphoma, or a carcinoma.
- 4. The method of claim 3, wherein the carcinoma is a carcinoma of the breast, prostate, ovary, endometrium, colon, stomach, liver, pancreas, esophagus, lung, oral mucosa, or skin.
- 5. The method of claim 1, wherein the beta-lactone is tetrahydrolipstatin, ebelactone A, or ebelactone B.
- 6. The method of claim 5, wherein the beta-lactone is tetrahydrolipstatin.
- 7. A method of inducing apoptosis of a cell that expresses fatty acid synthase in a subject, comprising administering an effective amount of a beta-lactone to the subject, thereby inducing apoptosis of the cell that expresses fatty acid synthase in the subject.
- 8. The method of claim 7, wherein the cell is a tumor cell.
- 9. The method of claim 7, wherein the cell overexpresses fatty acid synthase.
- 10. The method of claim 7, wherein the subject is identified as being in need of administration of a beta-lactone to induce apoptosis of a cell that expresses fatty acid synthase.
- 11. A method of inducing cell cycle arrest of a cell that expresses fatty acid synthase in a subject, comprising administering an effective amount of a beta-lactone to the subject, thereby inducing cell cycle arrest of the cell that expresses fatty acid synthase in the subject.
- 12. The method of claim 11, wherein the cell is a tumor cell.
- 13. The method of claim 11, wherein the cell overexpresses fatty acid synthase.
- 14. The method of claim 11, wherein the subject is identified as being in need of administration of a beta-lactone to induce cell cycle arrest of a cell that expresses fatty acid synthase.
- 15. The method of claim 11, wherein the beta-lactone is tetrahydrolipstatin, ebelactone A, or ebelactone B.
- 16. The method of claim 15, wherein the beta-lactone is tetrahydrolipstatin.
- 17. A method of treating a cancer of the intestinal mucosa in a subject, comprising:
a) identifying the subject as being in need of treatment with a beta-lactone to treat the cancer, and b) orally administering an effective amount of the beta-lactone to the subject, thereby treating the cancer of the intestinal mucosa in the subject.
- 18. A method of inhibiting angiogenesis in a subject, said method comprising administering an effective amount of an antagonist of fatty acid synthase to the subject, thereby inhibiting angiogenesis in the subject.
- 19. The method of claim 18, wherein the antagonist inhibits activity of the ketoacyl synthase domain of fatty acid synthase.
- 20. The method of claim 19, wherein the antagonist is cerulenin.
- 21. The method of claim 19, wherein the antagonist is c75.
- 22. The method of claim 18, wherein the antagonist inhibits activity of the thioesterase domain of fatty acid synthase.
- 23. The method of claim 22, wherein the antagonist is a beta-lactone.
- 24. The method of claim 23, wherein the beta-lactone is tetrahydrolipstatin, ebelactone A, or ebelactone B.
- 25. The method of claim 24, wherein the beta-lactone is tetrahydrolipstatin.
- 26. The method of claim 18, wherein angiogenesis is inhibited for the purpose of treating macular degeneration, diabetic retinopathy, arthritis, obesity, psoriasis, eczema, scleroderma, a haemangioma, an angiosarcoma, or Kaposi's sarcoma.
- 27. The method of claim 23, wherein angiogenesis is inhibited for the purpose of treating a tumor.
- 28. A method of identifying a beta-lactone that inhibits tumor cell proliferation, comprising:
a) contacting a sample comprising fatty acid synthase with a beta-lactone, and b) measuring fatty acid synthase activity in the sample, whereby a decrease in the amount of fatty acid synthase activity in the sample, relative to the amount of fatty acid synthase activity in a sample not contacted with the beta-lactone, identifies a beta-lactone that inhibits tumor cell proliferation.
- 29. The method of claim 28, wherein the compound induces cell cycle arrest of a tumor cell.
- 30. The method of claim 28, wherein the compound induces apoptosis of a tumor cell.
- 31. A method of identifying a beta-lactone that inhibits tumor cell proliferation, comprising:
a) contacting a sample comprising tumor cells with a beta-lactone, and b) measuring the amount of cell proliferation, cell cycle progression, cell cycle arrest, or apoptosis in the sample exposed to the beta-lactone, whereby a decrease in cell proliferation, a decrease in cell cycle progression, an increase in cell cycle arrest, or an increase in apoptosis in the sample comprising tumor cells exposed to the beta-lactone, relative to the amount of proliferation, cell cycle progression, cell cycle arrest, or apoptosis in a sample comprising tumor cells not contacted with the beta-lactone, identifies a beta-lactone that inhibits proliferation of a tumor cell.
- 32. A method of identifying a compound that inhibits angiogenesis, comprising:
a) contacting a sample comprising fatty acid synthase with the compound, and b) measuring fatty acid synthase activity in the sample, whereby a decrease in the amount of fatty acid synthase activity in the sample, relative to the amount of fatty acid synthase activity in a sample not contacted with the compound, identifies a compound that inhibits angiogenesis.
- 33. The method of claim 32, wherein the compound is a beta-lactone.
- 34. A method of identifying a beta-lactone that inhibits angiogenesis, comprising:
a) contacting a sample comprising endothelial cells with a beta-lactone, and b) measuring the amount of endothelial cell proliferation, cell cycle progression, or cell cycle arrest in the sample, whereby a decrease in cell proliferation, a decrease in cell cycle progression, or an increase in cell cycle arrest in the sample, relative to the amount of cell proliferation, cell cycle progression, or cell cycle arrest in a sample comprising endothelial cells not contacted with the beta-lactone, identifies a beta-lactone that inhibits angiogenesis.
- 35. A method of identifying a beta-lactone that inhibits angiogenesis, comprising:
a) contacting a sample with the beta-lactone, wherein the sample comprises angiogenic cells, and b) measuring the amount of angiogenesis in the sample, whereby a decrease in the amount of angiogenesis in the sample, relative to the amount of angiogenesis in a sample not contacted with the beta-lactone, identifies a beta-lactone that inhibits angiogenesis.
- 36. The method of claim 1, 7, 11, 17, 23, 28, 31, 33, 34, or 35, wherein the beta-lactone has the formula I:
- 37. The method of claim 1, 7, 11, 17,23, 28, 31, 33, 34, or 35, wherein R1 is a straight chain alkyl group.
- 38. The method of claim 17, wherein the beta-lactone is tetrahydrolipstatin, ebelactone A, or ebelactone B.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of priority from U.S. Provisional Application Serial No. 60/373,181, filed Apr. 17, 2002, which application is hereby incorporated by reference in its entirety.
STATEMENT OF FEDERALLY SPONSORED RESEARCH
[0002] This invention was made with government support under Grant No. CA 69036 awarded by the National Institutes of Health. The government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60373181 |
Apr 2002 |
US |