title: Altered DNA binding and amplification of human breast cancer suppressor gene BRCA1 induced by a novel antitumor compound, [Ru(η(6)-p-phenylethacrynate)Cl(2)(pta)].
abstract: The ruthenium-based complex [Ru(η(6)-p-phenylethacrynate)Cl(2)(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane), termed ethaRAPTA, is an interesting antitumor compound. The elucidation of the molecular mechanism of drug activity is central to the drug development program. To this end, we have characterized the ethaRAPTA interaction with DNA, including probing the sequence specific modified DNA structural stability and DNA amplification using the breast cancer suppressor gene 1 (BRCA1) of human breast and colon adenocarcinoma cell lines as models. The preference of ethaRAPTA base binding is in the order A > G > T > C. Once modified, the ethaRAPTA-induced BRCA1 structure has higher thermal stability than the modified equivalents of its related compound, RAPTA-C. EthaRAPTA exhibits a higher efficiency than RAPTA-C in inhibiting BRCA1 amplification. With respect to both compounds, the inhibition of BRCA1 amplification is more effective in an isolated system than in cell lines. These data provide evidence that will help to understand the process of elucidating the pathways involved in the response induced by ethaRAPTA.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences,  Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand. adisorn.r@psu.ac.th.
authors.forename: Korawan
authors.initials: K
authors.lastname: Chakree
authors.forename: Chitchamai
authors.initials: C
authors.lastname: Ovatlarnporn
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Adisorn
authors.initials: A
authors.lastname: Ratanaphan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D000081007:Cymenes; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D000081007:Cymenes; D018736:DNA Adducts; D009942:Organometallic Compounds; C530402:dichloro(4-cymene)(1,3,5-triaza-7-phosphatricyclo(3.3.1.1)decane)ruthenium(II); D004247:DNA