Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer

Nutr Cancer. 2015;67(7):1159-69. doi: 10.1080/01635581.2015.1068819. Epub 2015 Aug 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / diet therapy*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Dietary Supplements*
  • Female
  • Lapatinib
  • Mice, Inbred BALB C
  • Quinazolines / administration & dosage
  • Receptor, ErbB-2 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Antioxidants
  • Quinazolines
  • Lapatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2