Hydroxytyrosol and oleuropein compositions for induction of DNA damage, cell death and LSD1 inhibition
Compositions comprising hydroxytyrosol-containing formulations and treatment regiments comprising hydroxytyrosol and/or oleuropein and chemotherapeutic agents are disclosed. Compositions and/or regiments may optionally include the administration of vitamins, minerals, and anti-oxidants. Methods for using these compositions and treatment regimens for treating subjects for diseases, such as a malignancy, and for inducing or enhancing angiogenesis, treating or preventing oxidative stress, for treating or preventing high glucose-induced dysfunction, treating or preventing chemotherapy-induced dysfunction, and for improving cell viability are provided. Various methods for use of the hydroxytyrosol compositions for inhibition of lysine specific demethylase 1 (LSD1) in various cancers are also provided.
1. A method of screening an individual or a cell of an individual for Lysine Specific Demethylase 1 (LSD1) linked cancer or pre-cancer comprising,
a) administering to said individual or said cell a composition comprising hydroxytyrosol, a hydroxytyrosol derived and/or substituted compound, and/or a hydroxytyrosol metabolite selected from the group consisting of:
(i) hydroxytyrosol that is isolated, purified and/or synthesized and has the following formula:
(ii) a hydroxytyrosol acyl derivative according to the following structure:
and
(iii) hydroxytyrosol derived and/or substituted compound and/or hydroxytyrosol metabolite has
wherein R1, R2, and R3 provide a pharmaceutically acceptable salt, solvate, prodrug and/or isomer of hydroxytyrosol; and
b) assaying for LSD1 linked cancer cell growth, proliferation and/or death; alteration of expression of an LSD1 gene; LSD1 linked cancer cell invasion, migration or adhesion and/or expression of LSD1 linked cancer cell markers in said individual or cell.
2. The method of claim 1 , wherein said assay comprises assaying for inhibition of LSD1.
3. The method of claim 1 wherein R1, R2 and R3 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, ORa, SRa, SORa, SO2Ra, OSO2Ra, OSO3Ra, NO2, NHRa, N(Ra)2, ═N—Ra, N(Ra)CORa, N(CORa)2, N(Ra)SO2Ra, N(Ra)C(═NRa)N(Ra)Ra, CN, halogen, CORa, COORa, OCORa, OCOORa, OCONHRa, OCON(Ra)2, CONHRa, CON(Ra)2, CON(Ra)ORa, CON(Ra)SO2Ra, PO(ORa)2, PO(ORa)Ra, PO(ORa)(N(Ra)Ra) and aminoacid ester having inhibitory efficacy against the LSD1 protein; and further wherein each of the Ra groups is independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, and the like having inhibitory efficacy against the LSD1 protein; and further wherein each of the substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and/or acyl groups are C1-28 (including all ranges therein).
4. The method of claim 1 , wherein said method comprises administering said composition to an individual.
5. The method of claim 1 , wherein said method comprises administering said composition to a cell.
6. The method of claim 1 , comprising assaying for cell death.
7. The method of claim 1 , comprising assaying for cell proliferation.