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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Role of Nuclear Factor Erythroid 2-Related Factor 2 (NRF-2) Mediated Antioxidant Response on the Synergistic Antitumor Effect of L-Arginine and 5-Fluro Uracil (5FU) in Breast Adenocarcinoma

Author(s): Asis Bala* and Shravani Sripathi Panditharadyula

Volume 25 , Issue 14 , 2019

Page: [1643 - 1652] Pages: 10

DOI: 10.2174/1381612825666190705205155

Price: $65


Breast adenocarcinoma (BAC) in glandular tissue cells have excessive metastasis and invasion capability. The major challenges for the chemotherapy used for the management of BAC include chemoresistance and auto-immunosuppression in BAC. The 5-fluro uracil (5-FU) based therapy promotes the immune activation in BAC by targeting the regulatory T cells and myeloid-derived suppressor cells (MDSC). The beneficial effect of the combination of L-Arginine with 5-FU strives to be established in different pre-clinical and clinical conditions and explored in the scientific literature. L-Arginine induces NO production and potentiates the anticancer effect of 5-FU. NO-mediated signaling is regulated by nuclear factor erythroid 2-related factor 2 (NRF-2) mediated antioxidant response. NRF-2 mediated antioxidant mechanism always suppresses the formation of superoxide (O2 -) as well as other reactive oxygen species (ROS). Thus the utilization of NO by O2 - will be minimum in this combination therapy. The regulatory role of NRF-2 in regulation to Antioxidant Response Element (ARE) mediated cytoprotective gene expression in BAC remains unexplored. The present review summarizes the role of NRF-2 mediated antioxidant response on the synergistic antitumor effect of L-Arginine and 5-FU in BAC. This review brought new insight into the management of BAC and in the same context, a hypothesis is raised on the use of reduced glutathione (GSH) or N-Acetyl Cysteine as it may be an added adjuvant in the combination of 5- FU and L-Arginine for management of BAC.

Keywords: Nuclear factor erythroid 2-related factor 2 (NRF-2), 5-fluro uracil, L-arginine, chemo-resistance, immunopharmacology, breast adenocarcinoma.

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