## 1 Introduction  
In the last two decades, nutrition as a science has progressed in an exponential way. Food is no longer the provider of nutrients, the energy workers of life sustaining functions of body growth and homeostasis, but rather one fundamental cornerstone in the complex network mechanism of the human body, both in health and disease [1]. Nutritional science uncovered innumerous research fields with extraordinary impact in human life and disease, like microbiome, food nanotechnology, public health (like preventive intervention against several chronic diseases), and specific nutrition niches like the ones used in sports and in clinical environment. One emerging field of nutrition is associated with functional foods: foods that promote a beneficial effect in the human metabolic functions [2]. Our work focused on pomegranate (_Punica granatum_), a widely consumed fruit with extraordinary health benefits and used since ancient civilizations [3]. Pomegranate plant is composed of different constituents (like the fruit, steams, leaves, flowers, or roots) which exert diverse pharmacologic activities and contain different polyphenol profile [3]. Within the present study, our focus was the external peel, since it represents about 50% of the fruit weight and is usually rejected to waste, regardless of its high levels of polyphenols and strong antioxidant capacity [4]. The family of phenolic compounds is a heterogeneous group of natural antioxidants and chemopre agents found in the human diet [5]. The pomegranate peel is mainly composed of gallic acid, epigallocatechin gallate, quercetin, rutin, anthocyanin, and other flavanols, flavones, and flavanones [3]. Furthermore, the synergetic action of the global components seems to outperform the performance of the individual components when taken separately [6]. Polyphenols from pomegranate peel are involved in many wide-ranging molecular pathways due to their antioxidant, anti-inflammatory, antimicrobial, anti-obesogenic, and anticarcinogenic properties and they interfere in pathologies like diabetes and metabolic syndrome [7], cardiovascular diseases [8], male infertility [9], Alzheimer's [10], and some types of cancer [11]. All these pathologies share a common hallmark in which the polyphenols play an important role: oxidative stress. Oxidative stress and its associated pathways are responsible for the balance of reactive oxygen species (ROS). Excessive accumulation of ROS can lead to DNA damage, amino acid oxidation, protein damage, and lipid peroxidation, which subsequently cause cytotoxicity/dysmetabolism and subsequently cancer [12]. Breast cancer (BC) is frequently found as a model in the literature to investigate the potential protective effect of fruit extracts. Polyphenols have a significant role to play, not only because of the aforementioned mechanisms, which are applicable to all types of cancers, but they may also exert additional hormonal dependent functions like interfering with aromatase enzyme by disrupting estrogen synthesis [13]. Without overlooking that BC is still one of the most common cancers and the most frequent among women, it is a complex, heterogeneous pathology [14] and has been a recurrent research model in how oxidative stress can modulate cancer etiology. Polyphenol-rich fruits have been frequently used in research as therapeutical agents in breast cancer with positive results [15]. Several studies have already demonstrated a correlation between pomegranate and antitumoral activity [16]. Results from in vitro studies conducted on several cell lines and using different pomegranate constituents have demonstrated its potential to decrease cell growth, proliferation, and modulate the inflammatory response. This suggests that pomegranate may exert anti-proliferative, anti-metastatic, anti-estrogenic, and pro-apoptotic effects [16]. While numerous studies have examined the outcomes of pomegranate extract, only a limited number have assessed the intracellular cascade linked to antioxidant enzymes.