Method for treatment of tumors using nordihydroguaiaretic acid derivatives

A method of stimulating apoptosis in a cell expressing CDC-2 and survivin comprising administering an effective amount of a compound of formula

• wherein R1, R2, R3 and R4 independently represent —OH, OCH3,—O(C=O)CH3, or an amino acid residue, but are not each —OH simultaneously.

A method for treating tumor in an animal, comprising the step of injecting into the tumor, more than once, an effective amount of at least one compound of the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said tumor.

A method of inhibiting growth of rapidly proliferating cells containing cyclin dependent kinase CDC2, comprising the step of injecting into a cell mass containing the rapidly proliferating cells at least one compound of the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously.

A method of inhibiting Sp1 regulated promoter activity in a proliferating cell comprising the step of contacting the promoter with at least one compound of the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said cell.

A method of up-regulating the expression of a cell cycle related gene in a cell, wherein the cell cycle related gene is selected from the group consisting of:

• cyclin-dependent kinase inhibitor, apoptosis antigen APO-1, death domain three DR3, ras-related protein RAP-1, and human Map Kinase, comprising the step of allowing the cell to contact at least one compound of the formula:
• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said cell.

A method of down-regulating the expression of a cell cycle related gene in a cell, wherein the cell cycle related gene is selected from the group consisting of cyclin-dependent kinase 7, cytokine receptor, proliferating cell nuclear antigen PCNA, TNF-related apoptosis APO2, and cysteine protease, comprising the step of allowing the cell to contact a compound of the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said tumor.

A method of inhibiting cyclin-dependent kinase CDC2 activity in a cell comprising contacting the cell with an effective amount of a compound of the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said tumor.

A method of treating tumor in an animal comprising the step of administering an effective amount of at least one compound by injection and targeted delivery to the tumor site, wherein the compound has the formula:

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said tumor.

A method of treating tumor in an animal comprising the step of administering an effective amount of at least one compound by systemic delivery to the subject, wherein the compound has the formula

• wherein R1, R2, R3 and R4 independently represent -OH, -OCH3, -O(C=O)CH3, or an amino acid residue or substituent or salt thereof, but are not each -OH simultaneously, to said tumor.

A method of treating tumor in an animal comprising the step of administering to the animal an effective amount of at least one compound, wherein the compound has the formula:

• wherein R1, R2, R3 and R4 are identical and represent an amino acid residue or substituent or salt thereof, wherein the amino acid residue or substituent is selected from the group consisting of alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, 5-hydroxylysine, 4-hydroxyproline, thyroxine, 3-methylhistidine, ∈-N-methyllysine, ∈-N,N,N-trimethyllysine, aminoadipic acid, γ-carboxyglutamic acid, phosphoserine, phosphothreonine, phosphotyrosine, N-methylarginine, and N-acetyllysine.