title: Cytotoxic activity of octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives in human breast cancer cells.
abstract: Evaluation of the cytotoxicity of novel octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives (1a-2c) employing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and inhibition of [(3)H]thymidine incorporation into DNA demonstrated that these compounds were more active than etoposide and camptothecin in both MDA-MB-231 and MCF-7 human breast cancer cells. Flow cytometric analysis after Annexin V-FITC and propidium iodide staining also confirmed that apoptosis was the main response of human breast cancer cells to 1a-2c treatment. Our results suggest that apoptosis of human breast cancer cells in the presence of 1a-2c follows the mitochondrial pathway, with the decrease in mitochondrial membrane potential and activation of caspase 9, as well as by the external pathway with the significant increase in caspase 8 expression. Cytotoxic properties of compounds 1a-2c in cultured human breast cancer cells correlate to their ability to inhibit topoisomerase I/II.
authors: Department of Biotechnology, Medical University of Białystok, Kilińskiego 1, 15-089, Białystok, Poland.
authors: Monika
authors: M
authors: Lepiarczyk
authors: Zbigniew
authors: Z
authors: Kałuża
authors: Anna
authors: A
authors: Bielawska
authors: Robert
authors: R
authors: Czarnomysy
authors: Agnieszka
authors: A
authors: Gornowicz
authors: Krzysztof
authors: K
authors: Bielawski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000633:toxicity*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D011719:Pyrazines / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D007546:Isoquinolines; D011719:Pyrazines; C039109:isoquinoline