Methods and use of inducing apoptosis in cancer cells

Abstract

The present disclosure relates to a method of inducing apoptosis in a cancer cell by delivery of exogenous Coenzyme Q10 or its metabolites thereof in a pharmaceutically acceptable carrier to effectuate cell contact of endogenous Coenzyme Q10 or its metabolites thereof in addition to but not limited to mevalonic acid and oleic acid to form an intracellular complex. The present disclosure also provides a method of modulating the p53 pathway and Bcl-2 protein family in a manner that restores the apoptotic potential to a cancer cell by delivery of Coenzyme Q10 in a pharmaceutically acceptable carrier. The present disclosure further provides a method to specifically normalize the ratio of pro-apoptotic and anti-apoptotic members of the Bcl-2 gene family in a proportion to re-program a cancer cell to undergo apoptosis.

1 . A method comprising:
 administering to a cell a composition comprising a liposome comprising a phospholipid and a bioactive agent comprising coenzyme Q10 or its metabolites; and   allowing the coenzyme Q 10 or its metabolites to form a complex with endogenous coenzyme Q10 and membrane lipids,   wherein the formation of the complex induces the cell to undergo apoptosis.   
     
     
         2 . The method of  claim 1 , wherein the membrane lipids comprise endogenous lipids selected from the group consisting of oleic acid, mevalonic acid and quinones. 
     
     
         3 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier, and wherein the coenzyme Q10 is present in an amount of from about 0.001% to about 60% (w/w) of the composition. 
     
     
         4 . The method of  claim 1 , wherein the composition is in a form selected from the group consisting of gels, ointments, creams, salves, lotions, mousses, foams, sprays, aerosols, liquids, nebulized powders, and suppositories. 
     
     
         5 . The method of  claim 1 , wherein the formation of the complex induces modulation of a cell protein selected from the group consisting of p53, Bcl-2, Bcl-2 subfamily members, and Bak. 
     
     
         6 . The method of  claim 5 , wherein modulation of the cell protein comprises re-activation of the p53 protein. 
     
     
         7 . The method of  claim 5 , wherein modulation of the cell protein comprises modulating at least one BH3 binding domain of the Bcl-2 family. 
     
     
         8 . The method of  claim 7 , wherein the at least one BH3 binding domain of the Bcl-2 family is selected from the group consisting of Bid, Bim, Bik, and combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the cell is an oncogenic cell. 
     
     
         10 . A method for treating cancer comprising:
 administering to an oncogenic cell a composition comprising a liposome comprising a phospholipid and a bioactive agent comprising coenzyme Q10 or its metabolites; and   allowing the coenzyme Q 10 or its metabolites to form a complex with endogenous coenzyme Q10 and membrane lipids,   wherein the formation of the complex modulates angiogenic factors of the oncogenic cell.   
     
     
         11 . The method of  claim 10 , wherein the membrane lipids comprise endogenous lipids selected from the group consisting of oleic acid, mevalonic acid and quinones. 
     
     
         12 . The method of  claim 10 , wherein the composition further comprises a pharmaceutically acceptable carrier, and wherein the coenzyme Q10 is present in an amount of from about 0.001% to about 60% (w/w) of the composition. 
     
     
         13 . The method of  claim 10 , wherein the composition is in a form selected from the group consisting of gels, ointments, creams, salves, lotions, mousses, foams, sprays, aerosols, liquids, nebulized powders, and suppositories. 
     
     
         14 . The method of  claim 10 , wherein the formation of the complex modulates angiogenic factors selected from the group consisting of VEGF, FGF, Hif-1α, and angiostatin. 
     
     
         15 . A method for treating cancer comprising:
 administering to an oncogenic cell a composition comprising a liposome comprising a phospholipid and a bioactive agent comprising coenzyme Q10 or its metabolites; and   allowing the coenzyme Q 10 or its metabolites to form a complex with endogenous coenzyme Q10 and membrane lipids,   wherein the formation of the complex modulates cell-cycle factors of the oncogenic cell.   
     
     
         16 . The method of  claim 15 , wherein the membrane lipids comprise endogenous lipids selected from the group consisting of oleic acid, mevalonic acid and quinones. 
     
     
         17 . The method of  claim 15 , wherein the composition further comprises a pharmaceutically acceptable carrier, and wherein the coenzyme Q10 is present in an amount of from about 0.001% to about 60% (w/w) of the composition. 
     
     
         18 . The method of  claim 15 , wherein the composition is in a form selected from the group consisting of gels, ointments, creams, salves, lotions, mousses, foams, sprays, aerosols, liquids, nebulized powders, and suppositories. 
     
     
         19 . The method of  claim 15 , wherein the formation of the complex modulates cell-cycle factors selected from the group consisting of smad proteins, TGF-β, cyclin-dependent kinases, and PI3K/akt.