Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity

Toxicol In Vitro. 2004 Oct;18(5):629-37. doi: 10.1016/j.tiv.2004.02.010.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / toxicity*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / toxicity*
  • Drug Combinations
  • Drug Screening Assays, Antitumor
  • Electron Spin Resonance Spectroscopy
  • Female
  • Fullerenes / pharmacology*
  • Humans
  • Hydrogen Peroxide / chemistry
  • Hydroxyl Radical / analysis
  • Iron / chemistry
  • Spin Trapping

Substances

  • Antibiotics, Antineoplastic
  • Drug Combinations
  • Fenton's reagent
  • Fullerenes
  • fullerol C60(OH)22
  • Hydroxyl Radical
  • Doxorubicin
  • Hydrogen Peroxide
  • Iron
  • fullerene C60