METHODS AND USE OF INDUCING APOPTOSIS IN CANCER CELLS
The present disclosure relates to a method of inducing apoptosis in a cancer cell by delivery of exogenous Coenzyme Q1O or its metabolites thereof in a pharmaceutically acceptable carrier to effectuate cell contact of endogenous Coenzyme Q1O 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 Q1O 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 - 19 . (canceled)
20 . A method for monitoring a patient with a cancer comprising detecting expression levels of at least two markers in a tumor sample from the patient, wherein the patient has been administered Coenzyme Q10 for treating the cancer, and wherein the at least two markers are selected from the group of oncogenic markers consisting of Bcl-2; Bax; Bid; Bim; Bad; Bak; Mcl-1; Bcl-xl; Bcl-xs; Bcl-w; Bik; Bok; BimL; Bcl-2-related A1; Harakiri (Hrk); BCL2/adenovirus E1B 19 kDa protein-interacting protein 3(BNIP3); Blk; Noxa protein; Puma protein; vascular endothelial factor (VEGF); fibroblast growth factor (FGF)-1, FGF-2; Hif-α; angiostatin; transforming growth factor (TGF)-β; a smad; a cyclin-dependent kinase (CDK); a phosphoinositide-3 kinase (PI3K), caspase 3, and an Akt, thereby monitoring the patient.
21 . The method of claim 20 , wherein the at least two oncogenic markers are selected from the group consisting of Bcl-2, Bad, Bid, Bcl-xl, caspase 3, Bax, and Mcl-1.
22 . The method of claim 20 , wherein the at least two oncogenic markers are Bax and Bcl- 2 .
23 . The method of claim 20 , wherein the at least two oncogenic markers are Bax and Bid.
24 . The method of claim 20 , wherein the method of monitoring further comprises detecting activation of p53 protein in the tumor sample from the patient.
25 . The method of claim 20 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 50% different from a normalized oncogenic marker level.
26 . The method of claim 20 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 25% different from a normalized oncogenic marker level.
27 . The method of claim 20 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 10% different from a normalized oncogenic marker level.
28 . A method of treating cancer in a patient comprising:
administering to the patient with cancer a composition comprising a therapeutically effective dose of Coenzyme Q10; and
detecting expression levels of at least two markers in a tumor sample from the patient, wherein the at least two markers are selected from the group of oncogenic markers consisting of Bcl-2; Bax; Bid; Bim; Bad; Bak; Mcl-1; Bcl-xl; Bcl-xs; Bcl-w; Bik; Bok; BimL; Bcl-2-related A1; Harakiri (Hrk); BCL2/adenovirus E1B 19 kDa protein-interacting protein 3(BNIP3); Blk; Noxa protein; Puma protein; vascular endothelial factor (VEGF); fibroblast growth factor (FGF)-1, FGF-2; Hif-α; angiostatin; transforming growth factor (TGF)-β; a smad; a cyclin-dependent kinase (CDK); a phosphoinositide-3 kinase (PI3K), caspase 3, and an Akt, thereby treating cancer in the patient.
29 . The method of claim 28 , wherein the at least two oncogenic markers are selected from the group consisting of Bcl-2, Bad, Bid, Bcl-xl, caspase 3, Bax, and Mcl-1.
30 . The method of claim 28 , wherein the at least two oncogenic markers are Bax and Bcl-2.
31 . The method of claim 28 , wherein the at least two oncogenic markers are Bax and Bid.
32 . The method of claim 28 , further comprising detecting activation of p53 protein in the tumor sample from the patient.
33 . The method of claim 28 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 50% different from a normalized oncogenic marker level.
34 . The method of claim 28 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 25% different from a normalized oncogenic marker level.
35 . The method of claim 28 , wherein the expression level of at least one of the oncogenic markers detected in the tumor sample is less than 10% different from a normalized oncogenic marker level.
36 . A method of treating cancer in a patient comprising:
administering to the patient with cancer a composition comprising a therapeutically effective dose of Coenzyme Q10, wherein expression levels of at least two markers were previously detected in a tumor sample from the patient, and wherein the at least two markers are selected from the group of oncogenic markers consisting of Bcl-2; Bax; Bid; Bim; Bad; Bak; Mcl-1; Bcl-xl; Bcl-xs; Bcl-w; Bok; Bik; BimL; Bcl-2-related A1; Harakiri (Hrk); BCL2/adenovirus E1B 19 kDa protein-interacting protein 3(BNIP3); Blk; Noxa protein; Puma protein; vascular endothelial factor (VEGF); fibroblast growth factor (FGF)-1, FGF-2; Hif-α; angiostatin; transforming growth factor (TGF)-β; a smad; a cyclin-dependent kinase (CDK); a phosphoinositide-3 kinase (PI3K), caspase 3, and an Akt, thereby treating cancer in the patient.
37 . The method of claim 36 , wherein the at least two oncogenic markers are selected from the group consisting of Bcl-2, Bad, Bid, Bcl-xl, caspase 3, Bax, and Mcl-1.
38 . The method of claim 36 , wherein the at least two oncogenic markers are Bax and Bcl-2.
39 . The method of claim 36 , wherein the at least two oncogenic markers are Bax and Bid.