title: Sulforaphane potentiates RNA damage induced by different xenobiotics.
abstract: BACKGROUND
  The isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage.
  
  
  RESULTS
  We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in different chronic diseases. Considering the ability of SFN to protect from genotoxicity, we also examined whether SFN is able to protect from RNA damage induced by different chemicals (doxorubicin, spermine, S-nitroso-N-acetylpenicillamine, H(2)O(2)). We observed that SFN was devoid of either RNA damaging and RNA protective activity in human leukemic cells. It was able to potentiate the RNA damage by doxorubicin and spermine. In the first case, the effect was attributable to its ability of modulating the bioreductive activation of doxorubicin. For spermine, the effects were mainly due to its modulation of ROS levels produced by spermine metabolism. As to the cytotoxic relevance of the RNA damage, we found that the treatment of cells with a mixture of spermine or doxorubicin plus SFN increased their proapoptotic potential. Thus it is conceivable that the presence of RNA damage might concur to the overall toxic response induced by a chemical agent in targeted cells.
  
  
  CONCLUSIONS
  Since RNA is emerging as a potential target for anticancer drugs, its ability to enhance spermine- and doxorubicin-induced RNA damage and cytotoxicity could represent an additional mechanism for the potentiating effects of SFN associated with anticancer drugs.
authors.affiliation: Department of Pharmacology, Alma Mater Studiorum - University of Bologna, Bologna, Italy. carmela.fimognari@unibo.it
authors.forename: Carmela
authors.initials: C
authors.lastname: Fimognari
authors.forename: Monia
authors.initials: M
authors.lastname: Lenzi
authors.forename: Piero
authors.initials: P
authors.lastname: Sestili
authors.forename: Eleonora
authors.initials: E
authors.lastname: Turrini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ferruzzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cantelli-Forti
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D017879:Isothiocyanates; D019169:Jurkat Cells; D012313:RNA / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D015262:Xenobiotics; D013096:Spermine; D012313:RNA; D013880:Thioredoxin-Disulfide Reductase; C016766:sulforaphane