title: Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity.
abstract: Paper presents the effects of the newly synthesized fullerol C60(OH)22 on the growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)-induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance (ESR) "trapping" method was used to investigate OH-radical scavenger activity of fullerol during Fenton's reaction. At a range of nanomolar concentrations fullerol induced cell growth inhibition, which was cell line, dose and time dependent. Fullerol also strongly suppressed DOX-induced cytotoxicity at all concentrations regardless the time of fullerol addition. Proanthocyanidins added as single agent to MCF-7 cell culture for 48 h induced low growth inhibition but in combination with DOX strongly decreased DOX cytotoxicity. Fullerol was found to be a potent hydroxyl radical scavenger: the relative intensity of ESR signals of DMPO-hydroxyl radical (DMPO-OH) spin adduct decreased by 88% in the presence of 0.5 microg/ml of fullerol. The obtained results suggest that antiproliferative effect of the fullerol and its protective effect on DOX-induced cytotoxicity might be mediated through hydroxyl-radical scavenger activity of C60(OH)22.
authors.affiliation: Institute of Oncology Sremska Kamenica, Institutski put 4, 21204 Sremska Kamenica, Serbia and Montenegro. gordanab@ptt.yu
authors.forename: Gordana
authors.initials: G
authors.lastname: Bogdanović
authors.forename: Vesna
authors.initials: V
authors.lastname: Kojić
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Dordević
authors.forename: Jasna
authors.initials: J
authors.lastname: Canadanović-Brunet
authors.forename: Mirjana
authors.initials: M
authors.lastname: Vojinović-Miloradov
authors.forename: Vladimir Vit
authors.initials: VV
authors.lastname: Baltić
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D037741:Fullerenes / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical / Q000032:analysis; D007501:Iron / Q000737:chemistry; D019097:Spin Trapping
chemical_list: D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; C045076:Fenton's reagent; D037741:Fullerenes; C496652:fullerol C60(OH)22; D017665:Hydroxyl Radical; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D007501:Iron; C069837:fullerene C60