Prenylated isoflavones for treatment of subjects with multidrug-resistant cancer

1. A method for treating a subject suffering from a multidrug-resistant cancer, wherein the cancer is resistant against at least one of taxol or doxorubicin and selected from a multidrug-resistant lung cancer, multidrug-resistant breast cancer, or multidrug-resistant colon cancer, comprising the step of administering an effective amount of a prenylated isoflavone or a pharmaceutically tolerable salt, solvate or anhydrate thereof to the subject, wherein the prenylated isoflavone is based on the general structure of Formula (I):

wherein compared to the general structure of Formula (I) the prenylated isoflavone:

(i) contains at least one prenyl-group attached to a carbon atom in ring A of the general structure of Formula (I); and

(ii) is optionally further modified by at least one of hydroxylation, alkylation, esterification, glycosylation, glucuronidation or hydrogenation.

2. The method of claim 1 , wherein the subject is a human and the multidrug-resistant cancer is a multidrug-resistant ABC-protein-dependent cancer.

3. The method of claim 1 , wherein the subject is a human and the multidrug-resistant cancer is a multidrug-resistant P-glycoprotein-dependent cancer.

4. The method of claim 1 , wherein the prenylated isoflavone has a structure of Formula (II):

with R 1 being hydrogen or —OH.

5. The method of claim 1 , wherein the prenylated isoflavone has the structure of Formula (III):

6. The method of claim 1 , wherein the prenylated isoflavone is administered in combination with an effective amount of at least one chemotherapeutic compound which is a substrate for P-glycoprotein, which chemotherapeutic compound is a compound selected from the group consisting of a topoisomerase-II inhibitor, an anthracycline, a coordination complex of platinum, a taxane, a protein kinase inhibitor, a vinca alkaloid or derivative thereof, a topoisomerase-I inhibitor and a nucleotide analog or precursor analog.

7. The method of claim 6 , wherein the prenylated isoflavone has a structure of Formula (III):

and wherein the chemotherapeutic compound is selected from taxol or doxorubicin.

8. The method of claim 6 , wherein the chemotherapeutic compound is administered before, after or simultaneously with the prenylated isoflavone.

9. A method for specifically targeting cancer cells with multidrug-resistance, wherein the cancer cells are resistant against at least one of taxol or doxorubicin and selected from multidrug-resistant lung cancer cells, multidrug-resistant breast cancer cells, or multidrug-resistant colon cancer cells, comprising the step of contacting a population of cancer cells with multidrug-resistance with a prenylated isoflavone or a salt, solvate or anhydrate thereof, wherein the prenylated isoflavone is based on the general structure of Formula (I):

and wherein compared to the general structure of Formula (I) the prenylated isoflavone:

(i) contains at least one prenyl-group attached to a carbon atom in ring A of the general structure of Formula (I); and

(ii) is optionally further modified by at least one of hydroxylation, alkylation, esterification, glycosylation, glucuronidation or hydrogenation.

10. The method of claim 9 , wherein the multidrug-resistant cancer cells are multidrug-resistant P-glycoprotein-dependent cancer cells and wherein the prenylated isoflavone inhibits P-glycoprotein.

11. The method of claim 9 , wherein the growth of the multidrug-resistant cancer cells is suppressed or cell death of the multidrug-resistant cancer cells is induced.

12. The method of claim 9 , wherein the prenylated isoflavone has a structure of Formula (III):

and wherein the cancer cells are contacted with between 5 μM and 30 μM of said prenylated isoflavone.

13. A method of potentiating the activity of a chemotherapeutic compound in multidrug-resistant cancer cells comprising contacting the multidrug-resistant cancer cells with

(i) a prenylated isoflavone; and

(ii) a chemotherapeutic compound, which chemotherapeutic compound is selected from the group consisting of a topoisomerase-II inhibitor, an anthracycline, a coordination complex of platinum, a taxane, a protein kinase inhibitor, a vinca alkaloid or derivative thereof, a topoisomerase-I inhibitor and a nucleotide analog or precursor analog; and

wherein the multidrug-resistant cancer cells are resistant against at least one of taxol or doxorubicin, wherein the multidrug resistant cancer cells are selected from multidrug-resistant lung cancer cells, multidrug-resistant breast cancer cells, or multidrug-resistant colon cancer cells, and wherein the prenylated isoflavone is based on the general structure of Formula (I):

wherein compared to the general structure of Formula (I) the prenylated isoflavone:

(i) contains at least one prenyl-group attached to a carbon atom in ring A of the general structure of Formula (I); and

(ii) is optionally further modified by at least one of hydroxylation, alkylation, esterification, glycosylation, glucuronidation or hydrogenation.

14. The method of claim 13 , wherein the multidrug-resistant cancer cells are contacted with the chemotherapeutic compound before, at the same time or subsequent to the application of the prenylated isoflavone.

15. The method of claim 13 , wherein the chemotherapeutic compound is taxol or doxorubicin.

16. The method of claim 13 , wherein the activity of the chemotherapeutic compound to inhibit proliferation or inducing cell death of the multidrug-resistant cancer cells is increased.

17. The method of claim 13 , wherein the prenylated isoflavone has the structure of Formula (III):

and the cells are contacted with between 4 μM and 20 μM of the prenylated isoflavone.