Effect of oncoxin oral solution in HER2-overexpressing breast cancer

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.This work was partially supported by Catalysis. Our Cancer Research Institute, and the work carried out at our laboratory receive support from the European Community through the regional development funding program (FEDER), and from the Fundación Ramón Areces.Peer Reviewe