title: Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer.
abstract: One of the most aggressive breast cancer subtypes includes tumors with high expression of HER2. Gene expression and functional studies have shown a link between HER2 overexpression and oxidative stress. Because of this, we hypothesized that Oncoxin Oral Solution (OOS), a composite product that contains several antioxidants, could have an antitumoral effect against HER2+ tumors. Dose-response studies, biochemical and cytometric assessment of the effect of OOS on cell cycle and apoptosis, and drug combination analyses were performed on BT474 and SKBR3 cells, 2 HER2-overexpressing breast cancer cell lines. OOS reduced the proliferation of these cells, and augmented the action of lapatinib, a HER2 inhibitor used in the breast cancer clinic. Moreover, OOS decreased growth of HER2+ tumors in mice. Mechanistically, OOS provoked cell cycle blockade through upregulation of p27 expression and downregulation of cyclin D levels. OOS also caused apoptotic cell death in HER2+ breast cancer cells, as indicated by increases in PARP cleavage as well as upregulation of caspase 8 and caspase 3 activities. These results demonstrate an antitumoral action of OOS in preclinical models of HER2+ breast cancer and suggest that it can be used with anti-HER2 therapies currently adopted as standard of care in the oncology clinic.
authors.affiliation: a Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca , Salamanca , Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Hernández-García
authors.affiliation: a Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca , Salamanca , Spain.
authors.forename: Verena
authors.initials: V
authors.lastname: González
authors.affiliation: b Catalysis SL , Madrid , Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sanz
authors.affiliation: a Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca , Salamanca , Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D005260:Female; D000077341:Lapatinib; D008807:Mice, Inbred BALB C; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000975:Antioxidants; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human