Suppression of cancer growth and metastasis using nordihydroguaiaretic acid derivatives with metabolic modulators

Abstract

Disclosed is a composition comprising a derivative of NDGA and at least one metabolic modulator. The composition can be in a unit dose form or kit. The composition can comprise at least two metabolic modulators. Also disclosed are methods for achieving cytotoxicity, particularly of rapidly dividing cells such as cancer, by administering a composition of the invention. In various embodiments of the invention subjects with cancer achieve prolonged survival and/or diminution in the size of their malignancies and cancer metastasis.

We claim: 
     
       1. A pharmaceutical anti-tumor composition comprising a synergistically effective amount of a derivative of nordihydroguaiaretic acid (NDGA) comprising tetra-o-methyl tetra-O-methyl nordihydroguaiaretic acid (M4N) or maltose-M3N and a synergistically effective amount of a metabolic modulator, wherein the metabolic modulator is selected from the group consisting of Ly294002, rottlerin, dichloroacetate, and rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus. 
     
     
       2. A method of treating a tumor, comprising administering to a mammal having said tumor an effective amount of the pharmaceutical composition of  claim 1 . 
     
     
       3. The method of  claim 2  wherein the tumor is selected from the group consisting of breast cancer, prostate cancer, lung cancer, colon cancer and ovarian cancer. 
     
     
       4. A method of inhibiting tumor growth in a mammal, said method comprising administering to said mammal a synergistically effective amount of a nordihydroguaiaretic acid (NDGA) derivative comprising tetra-o-methyl tetra-O-methyl nordihydroguaiaretic acid (M4N) or maltose-M3N; and a synergistically effective amount of a metabolic modulator, wherein the metabolic modulator is selected from the group consisting of Ly294002, rottlerin, dichloroacetate, and rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus. 
     
     
       5. The method of  claim 4  wherein the mammal is a human, cat, dog or mouse. 
     
     
       6. The method of  claim 4  wherein the tumor is selected from the group consisting of breast cancer, prostate cancer, lung cancer, colon cancer and ovarian cancer. 
     
     
       7. The method of claim 2 wherein the metabolic modulator is selected from: rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus. 
     
     
       8. The method of claim 3 wherein the metabolic modulator is selected from: rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus. 
     
     
       9. The method of claim 7 wherein the metabolic modulator is selected from: everolimus and temsirolimus. 
     
     
       10. The method of claim 9 wherein the metabolic modulator is everolimus. 
     
     
       11. The method of claim 4 wherein the metabolic modulator is selected from: rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus. 
     
     
       12. The method of claim 11 wherein the metabolic modulator is selected from: everolimus and temsirolimus. 
     
     
       13. The method of claim 12 wherein the metabolic modulator is everolimus. 
     
     
       14. The method of claim 6 wherein the metabolic modulator is selected from: rapamycin, and the water soluble derivatives of rapamycin, everolimus and temsirolimus.