Methods and use of inducing apoptosis in cancer cells
Inventors
Narain, Niven Rajin • Persaud, Indushekhar • McCook, John Patrick
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10668028-B2
Publication Date
2020-06-02
Expiration Date
Abstract
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.
Core Innovation
The disclosed invention provides an apoptosis-inducing cancer therapy by administering exogenous Coenzyme Q10 and/or metabolites to a patient. The therapy is described as forming an intracellular complex with endogenous Coenzyme Q10 and membrane lipids, including mevalonic acid and oleic acid, in a pharmaceutically acceptable carrier.
The disclosed invention further relates to modulating the p53 pathway and Bcl-2 family proteins to restore apoptotic potential. The described modulation includes normalizing pro-/anti-apoptotic Bcl-2 family protein ratios and associated apoptosis-related protein expression.
The document describes embodiments that include Coenzyme Q10 administration and detection or readouts of protein expression changes after Coenzyme Q10 treatment. Target proteins described include Bcl-2, Bax, Bid, Bim, Bik, Bcl-xl, Mcl-1, caspase-3, and additional pathway-associated markers such as VEGF/FGF/Hif-1α, TGF-β/Smad proteins, and PI3K/Akt.
Claims Coverage
The partial content provides one independent claim. The main inventive features cover administering a therapeutically effective dose of Coenzyme Q10 to a patient to normalize protein expression levels of specified oncogenic markers, followed by detecting marker protein expression in a post-administration tumor sample with a defined closeness to a normalized level.
Coenzyme Q10 administration for oncogenic marker normalization
Administering to a patient a composition comprising a therapeutically effective dose of Coenzyme Q10.
Post-administration tumor-sample detection within a normalization threshold
Detecting a protein expression level of the oncogenic markers Bcl-2, Bax and caspase 3 in a tumor sample obtained from the patient after administration of Coenzyme Q10 that is less than 50% different from a normalized oncogenic marker protein expression level, wherein the normalizing of the protein expression level is achieved by administering the composition comprising a therapeutically effective dose of Coenzyme Q10 to the patient.
Across the provided independent claim, normalization is achieved by administering a therapeutically effective dose of Coenzyme Q10 and confirming, in a post-administration tumor sample, that protein expression levels of Bcl-2, Bax, and caspase 3 are less than 50% different from a normalized level.
Stated Advantages
Restores apoptotic potential by modulating the p53 pathway and Bcl-2 family proteins.
Normalizes pro-/anti-apoptotic Bcl-2 family protein ratios.
Documented Applications
Apoptosis-inducing cancer therapy by administering Coenzyme Q10 or metabolites in a pharmaceutically acceptable carrier, including intracellular complex formation with endogenous CoQ10 and membrane lipids.
Use in a patient with cancer for normalizing protein expression levels of oncogenic markers Bcl-2, Bax, and caspase 3 by detecting marker expression in a tumor sample after Coenzyme Q10 administration.
Cancer evaluation supported by analyses across multiple cancer cell lines and a nude athymic mouse melanoma model, including protein expression readouts and histology.
Interested in licensing this patent?