title: Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells.
abstract: Free radicals are formed as a result of cellular processes and play a key role in predisposition to and development of numerous diseases and of premature aging. Recently, we reported the syntheses of a number of novel phenolic antioxidants for possible application in food industry. In the present study, analyses of the cellular processes and molecular gene expression effects of some of the novel antioxidants in normal human tissues and in cancer cells were undertaken. Results indicated that whereas the examined antioxidants showed no effects on morphology and gene expression of normal human oral and gingival epithelial tissues, they exerted a profound cell killing effect on breast cancer cells, including on chemotherapy-resistant breast cancer cells and on oral squamous carcinoma cells. Among the tested antioxidants, N-decyl-N-(3-methoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide and N-decyl-N-(3,5-dimethoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide were the most promising, with excellent potential for cancer treatment. Moreover, our gene expression databases can be used as a roadmap for future analysis of mechanisms of antioxidant action.
authors.affiliation: Department of Chemistry; University of Lethbridge; Lethbridge, AB Canada; Department of Biological Sciences; University of Lethbridge; Lethbridge, AB Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Kovalchuk
authors.forename: Felix
authors.initials: F
authors.lastname: Aladedunye
authors.forename: Rocio
authors.initials: R
authors.lastname: Rodriguez-Juarez
authors.forename: Dongping
authors.initials: D
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
authors.forename: Roman
authors.initials: R
authors.lastname: Przybylski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology / Q000633:toxicity*; D002109:Caffeic Acids / Q000494:pharmacology / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology / Q000633:toxicity; D008055:Lipids / Q000494:pharmacology / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D000076228:MRE11 Homologue Protein; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; C493956:CDKN1A protein, human; D002109:Caffeic Acids; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D062385:Hydroxybenzoates; D008055:Lipids; C121766:MRE11 protein, human; D018809:Proliferating Cell Nuclear Antigen; D000076228:MRE11 Homologue Protein; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: antioxidants; breast cancer; free radicals; gene expression; human 3D tissues; oral cancer
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