Unifying mechanism and methods to prevent cancer and neurodegenerative diseases

Abstract

The present invention relates to methods for preventing the development of cancer or neurodegenerative diseases by administering N-Acetylcysteine (NAC), melatonin, or a combination thereof. The present invention also relates to methods for diagnosing cancer and / or neurdegenerative disease by detecting or determining the amount of dopamine metabolites, 4-CE, 2-CE, methylation of CE or CE-Q conjugates.

Description

RELATED APPLICATION [0001] This application is a continuation-in-part under 35 U.S.C. 111(a) of International Application No. PCT / US03 / 007686 filed Mar. 12, 2003 and published in English as WO 03 / 077900 on Sep. 25, 2003, which claimed priority from Provisional Application No.60 / 364,544, filed Mar. 14, 2002, which applications and publication are incorporated herein by reference.GOVERNMENT FUNDING [0002] The invention described herein was made with government support under Grant Number PO1CA49210 and RO1CA49917 awarded by the National Cancer Institute, NIH. The United States Government has certain rights in the invention.BACKGROUND OF THE INVENTION [0003] Cancer is a disease that begins with mutation of critical genes: oncogenes and tumor suppressor genes. Mutation of critical genes allows for a cancer cell to evolve and ultimately results in pathogenic replication (a loss of normal regulatory control leading to excessive cell proliferation) of various given types of cells found in t...

AI Technical Summary

Benefits of technology

[0006] Applicant has discovered that oxidation of the carcinogenic 4-hydroxy catechol estrogens (CE) of estrone (E1) and estradiol (E2) to catechol estrogen-3,4-quinones (CE-3,4-Q) results in electrophilic intermediates that covalently bind to DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The resultant apurinic sites in critical genes can generate mutations that may initiate various human cancers. As such, the endogenous quinones, including CE-3,4-Q, may be endogenous tumor initiators. As yet, there are no treatment methods available that are specifically directed toward preventing the association of the metabolic intermediates, such as endogenous (that which has originated or been produced within an organism, tissue, or cell) quinones, with DNA, and thus, preventing excessive cell growth and the development / formation of cancer.

[0009] Applicant has also discovered that N-acetylcysteine (NAC) is capable preventing the formation of depurinating adducts (endogenous tumor initiators and / or neurodegenerative initiators) by aiding in the removal, detoxification and / or sequestration of, for example, catechol quinones and / or the oxidation products of benzene and dopamine prior to their association with DNA. Applicant has further discovered that NAC may be useful to prevent the formation of quinones.

[0010] Applicant has further discovered that melatonin is useful in the prevention of the formation of depurinating adducts, particularly those formed in the brain due to dopamine oxidation and the resultant production of its quinone.

[0011] Thus, Applicant has discovered that the use of NAC and / or melatonin can prevent or diminish the formation of depurinating adducts, and therefore, prevent and / or treat cancer and / or neurodegenerative disorders. Further, it is believed that practice of the invention will, at least in part, influence and control cellular mortality by allowing the cell to maintain a lower level of endogenous quinones (that have the ability to bind DNA and form depurinating adducts) and thus, allow the cell to follow a normal apoptotic pathway (programmed cell death, such as that signaled by the nuclei in normally functioning human and animal cells when age or state of cell health and condition dictates).

[0012] Accordingly, the present invention provides pharmaceutical compositions and methods to treat and / or prevent cancer and neurodegenerative diseases and for reducing cancer and neurodegenerative disease mortality. The present invention is further directed to methods of utilizing N-acetylcysteine (NAC) and melatonin to treat, prevent, and / or reduce the risk of cancer and neurodegenerative diseases and disorders, to reduce the formation of DNA adducts by reactive electrophilic estrogen metabolites, and / or to reduce the formation of DNA adducts by reactive electrophilic dopamine metabolites.

Problems solved by technology

As yet, there are no treatment methods available that are specifically directed toward preventing the association of the metabolic intermediates, such as endogenous (that which has originated or been produced within an organism, tissue, or cell) quinones, with DNA, and thus, preventing excessive cell growth and the development / formation of cancer.

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