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.

Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

“…In this context, OOS ® is a mixture which has shown to have promising antitumor results in different in vitro and in vivo cancer models (6–8); thus, it might be a suitable complement for irinotecan treatment in the progression of hepatic metastasis of CRC. Previously we have shown that OOS ® slows down the metastatic progression of CRC to the liver in vivo (7).…”

“…This compound has probed to possess antitumoral and immunomodulatory effects (6,7) and to potentiate the antiproliferative effect of standard chemotherapeutic agents in acute myeloid leukemia (8). Márquez et al (2016) showed that this nutrient mixture slows down the metastatic progression of CRC to the liver in an experimental model of metastatic development to the liver (7).…”

Antitumoral effect of Ocoxin in hepatocellular carcinoma

“…The proliferation of HCC cells was examined using a modified MTT metabolization assay (13). The cells were plated in triplicate and treated the next day as indicated, with various concentrations of OOS alone or in combination with other drugs: Sorafenib (LC Laboratories, Woburn, MA, USA) 0.1, 0.3, 1 or 3 µM; docetaxel (Hospira UK Ltd., Leamington Spa, UK) 1 or 3 µM; and cisplatin (Pharmacia Grupo Pfizer, Madrid, Spain) 2 and 20 µM.…”

“…Ocoxin® oral solution (OOS) is an oral nutritional supplement that contains several compounds with anticancer activities, including epigallocatechin-3 gallate (13). In addition, OOS is comprised of a variety of other components, including vitamins B6 and C and cinnamic acid, which exhibit anticancer properties (14–16).…”

“…As OOS contains several compounds with an antitumor action, it is currently being investigated in clinical trials as part of the treatment of several types of cancer, in which an improvement in the quality of life of the patients has been reported (18,19). Additionally, several recent reports have demonstrated that OOS exhibits in vitro and in vivo antitumoral action in various tumor models, including HER2 positive breast cancer (13) and acute myeloid leukemia (20). These two tumor types are dissimilar at the molecular and cellular levels; however, the clear antitumoral action of OOS has been reported in the two.…”