USE OF LIPID CONJUGATES IN THE TREATMENT OF CANCER
This invention provides for the use of compounds represented by the structure of the general formula (A): wherein L is a lipid or a phospholipid, Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol, Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, X is a physiologically acceptable monomer, dimer, oligomer, or polymer, wherein X is a glycosaminoglycan; and n is a number from 2 to 1000, wherein any bond between L, Z, Y and X is either an amide or an esteric bond in treating a subject suffering from a disease associated with elevated level of a Matrix Metalloprotease (MMP) such as a malignant cancer.
1 . A method for treating a subject afflicted with lung cancer, comprising the step of administering to said subject a composition comprising a compound represented by the structure of the general formula (I):
wherein
R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is glycosaminoglycan alginate or polygeline; and
n is a number from 1 to 1,000;
wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via an amide bond and if Y is a spacer, said spacer is directly linked to X via an amide or an esteric bond and to said phosphatidylethanolamine via an amide bond.
2 . The method of claim 1 , wherein said n is a number from 2 to 1,000.
3 . The method of claim 1 , wherein said glycosaminoglycan is selected from the group consisting of hyaluronic acid, heparin, heparan sulfate, chondrotin sulfate, keratan, keratan sulfate, dermatan sulfate or a derivative thereof.
4 . The method of claim 1 , wherein said phosphatidylethanolamine is a myristoyl or palmitoyl phosphatidylethanolamine.
5 . The method of claim 1 , wherein said phosphatidylethanolamine is a dipalmitoyl phosphatidylethanolamine, or dimyristoyl phosphatidylethanolamine.
6 . A method for attenuating invasiveness of a cancer cell, comprising the step of subjecting said cancer cell to a composition comprising a compound represented by the structure of the general formula (I):
wherein
R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is glycosaminoglycan, alginate or polygeline; and
n is a number from 1 to 1,000;
wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via an amide bond and if Y is a spacer, said spacer is directly linked to X via an amide or an esteric bond and to said phosphatidylethanolamine via an amide bond.
7 . The method of claim 6 , wherein said n is a number from 2 to 1,000.
8 . The method of claim 6 , wherein said glycosaminoglycan is selected from the group consisting of hyaluronic acid, heparin, heparan sulfate, chondrotin sulfate, keratan, keratan sulfate, dermatan sulfate or a derivative thereof.
9 . The method of claim 6 , wherein said phosphatidylethanolamine is a myristoyl or palmitoyl phosphatidylethanolamine.
10 . The method of claim 6 , wherein said phosphatidylethanolamine is a dipalmitoyl phosphatidylethanolamine, or dimyristoyl phosphatidylethanolamine.
11 . A method for inhibiting proliferation of an endothelial cell, comprising the step of subjecting said endothelial cell to a composition comprising a compound represented by the structure of the general formula (I):
wherein
R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is glycosaminoglycan, alginate or polygeline; and
n is a number from 1 to 1,000;
wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via an amide bond and if Y is a spacer, said spacer is directly linked to X via an amide or an esteric bond and to said phosphatidylethanolamine via an amide bond.
12 . The method of claim 11 , wherein said n is a number from 2 to 1,000.
13 . The method of claim 11 , wherein said glycosaminoglycan is selected from the group consisting of hyaluronic acid, heparin, heparan sulfate, chondrotin sulfate, keratan, keratan sulfate, dermatan sulfate or a derivative thereof.
14 . The method of claim 11 , wherein said phosphatidylethanolamine is a myristoyl or palmitoyl phosphatidylethanolamine.
15 . The method of claim 11 , wherein said phosphatidylethanolamine is a dipalmitoyl phosphatidylethanolamine, or dimyristoyl phosphatidylethanolamine.
16 . The method of claim 11 , wherein capillary formation is inhibited by inhibiting proliferation of said endothelial cell.