Chemopreventive effect of Pistacia vera leaf extract against Mammary Carcinoma Induced by Dimethyl-Benz(a)anthracene in vivo and in vitro: potential role of antioxidant, antiinflammatory and immune mechanisms

This study aimed to define the antitumor effect of ethanolic extract of Pistacia vera leaves (PEE) toward breast cancer both in vitro and in vivo using dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in adult female rats. PEE showed a potent antioxidant effect toward both DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radicals with IC₅₀ values of 72.6 and 107.4 μg/mL, respectively. PEE exerted its cytotoxicity in dose-dependent manners with favorable selectivity toward MCF-7 and MDA cancer cells, sparing normal WI-38 cells. Through considerable decreases in blood CA15.3, CEA, CA19.9, TNF-α, IL1β, IL-4, IL-6, and IL-10 levels, as well as mammary MDA and NO levels, PEE administration effectively improved the damage caused by breast cancer. Additionally, PEE exhibited remarkable increasing in mammary GSH content, GPx, SOD and CAT activities. The histopathological findings demonstrated the therapeutic potential of PEE that successfully improved the mammary gland alterations induced by DMBA and aborted cancer development. PEE has shown intriguing potential as an anti-inflammatory and antioxidant drug by targeting the expression of pro-inflammatory cytokines and oxidative stress indicators, which has helped to successfully treat malignancies in clinical settings. Collectively, our findings support chemo-preventive potential of PEE against DMBA-induced breast tumor in rats via enhancing apoptosis and immune response.