title: Lack of effect of coenzyme q10 on doxorubicin cytotoxicity in breast cancer cell cultures.
abstract: BACKGROUND/HYPOTHESES: Doxorubicin is a standard adjuvant therapy for early-stage breast cancer, and it significantly improves disease-free and overall survival. However, 3% to 20% of breast cancer patients develop chronic cardiomyopathic changes and congestive heart failure because of doxorubicin therapy. Doxorubicin-induced cardiotoxicity is thought to be due to the increased generation of reactive oxygen species within cardiac myocyte mitochondria. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that may protect against mitochondrial reactive oxygen species and thus prevent doxorubicin-induced cardiotoxicity. Despite the potential benefits of CoQ10 in preventing cardiotoxicity, it is not known if CoQ10 diminishes the antineoplastic effects of doxorubicin therapy.
  
  
  METHODS
  In vitro cell culture experiments.
  
  
  METHODS
  Breast cancer cell lines (MDA-MB-468 and BT549) were tested for their ability to uptake exogenous CoQ10 using high-performance liquid chromatography. Breast cancer cell lines were then treated with doxorubicin and a range of CoQ10 concentrations to determine the effect of CoQ10 on doxorubicin's cytotoxicity.
  
  
  RESULTS
  This study demonstrated that intracellular and mitochondrial CoQ10 concentrations increased substantially as higher exogenous concentrations were administered to breast cancer cells. CoQ10 had no effect on the ability of doxorubicin to induce apoptosis or inhibit growth or colony formation in both the cell lines tested when applied over a wide dose range, which encompassed typical basal plasma levels and plasma levels above those typically achieved by supplemented patients.
  
  
  CONCLUSIONS
  The clinical testing of CoQ10 as a supplement to prevent doxorubicin-induced cardiotoxicity requires confidence that it does not decrease the efficacy of chemotherapy. These results support the hypothesis that CoQ10 does not alter the antineoplastic properties of doxorubicin. Further in vivo studies, as well as combination chemotherapy studies, would be reassuring before a large-scale clinical testing of CoQ10 as a cardioprotective drug.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University.|Department of Medicine, College of Physicians and Surgeons, Columbia University.|Herbert Irving Comprehensive Cancer Center, Columbia University.
authors.forename: Heather
authors.initials: H
authors.lastname: Greenlee
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Shaw
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University.
authors.forename: Ying-Ka Ingar
authors.initials: YI
authors.lastname: Lau
authors.affiliation: Department of Neurology, Columbia University.
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University.|Herbert Irving Comprehensive Cancer Center, Columbia University.
authors.forename: Matthew
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D014451:Ubiquinone; D004317:Doxorubicin; C024989:coenzyme Q10