title: In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides.
abstract: In vitro cytotoxicity tests currently in use applied in the developmental stages of anticancer drug discovery are able to select the most potent compounds, but are not predictive of their potential toxicity. In this study, we have demonstrated the applicability of neutral red uptake assay using mouse fibroblasts Balb/c 3T3 cell line (3T3 NRU assay) for in vitro toxicity testing of newly synthesized genistein glycosides, the compounds that appear to show anticancer activity. We have also proven the compatibility of in-house 3T3 NRU assay with the prediction model for acute rodent oral toxicity testing, endorsed by NIEHS-ICCVAM workshop. The combined results from the cytotoxicity and the in vitro toxicity tests facilitated the selection of the most promising genistein derivatives, compounds G21 and G23, which were the most active and selective towards cancer cells. The comparison of predicted LD50 values revealed that almost all genistein derivatives are at least two-fold less toxic than the chemotherapeutics currently used in cancer therapy, which is very promising for this new group of compounds.
authors.affiliation: Flow Cytometry Laboratory National Institute of Public Health, Chelmska, 30/34, 00-725 Warsaw, Poland. joanpop@poczta.fm
authors.forename: Joanna
authors.initials: J
authors.lastname: Popiołkiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Polkowski
authors.forename: Janusz S
authors.initials: JS
authors.lastname: Skierski
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004396:Coloring Agents / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts; D019833:Genistein / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity*; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008962:Models, Theoretical; D009369:Neoplasms / Q000188:drug therapy; D009499:Neutral Red / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D004396:Coloring Agents; D009499:Neutral Red; D019833:Genistein