## 2 Pomergnate Health-Promoting Properties
### Anticancer Properties
The inhibition of cellular growth was already observed with an IC\({}_{50}\) amounting to 50 mg/mL in both the lines, but individual phytochemicals were slightly responsible for it. However, data showed increased proportion levels of cells lacking of CD44 and CD24 (connected with high tumor-initiating ability), demonstrating that PE can modify cell phenotypes, reducing the tumorigenicity [66]. [PERSON] and [PERSON] assessed the antioxidant and anticancer properties of different PEs, highlighting that the peel extract possesses the best antioxidant activity with an IC\({}_{50}\) value of 0.50 \(\pm\) 0.9 mg/mL, and promising anticancer action toward MCF-7 breast cancer cells and HCT-116 colon cancer with IC\({}_{50}\) values of 7.7 \(\pm\) 0.01 and 9.3 \(\pm\) 0.06 mg/mL, respectively [67]. In 2015, [PERSON] and co-workers investigated the possible antitumor activity of two different extracts of _Punica Granatum_ grown in Saudi Arabia. Their findings evidenced a good percentage of cellular growth inhibition at the maximum concentration tested (100 mg/mL) from both seeds and husks extracts, tested on hepatocellular carcinoma HepG2 (values amounting to 95.8 and 98.3%, respectively) and colon cancer CACO cells (values amounting to 99 and 97%, respectively). The whole cytotoxic profile exhibited a dose-dependent trend. The percentages of cellular growth inhibition permitted to determinate the corresponding IC\({}_{50}\) values. They were 45 and 40 mg/mL on both HepG2 and CACO cells for pomegranate seeds and husks extracts, respectively [68]. Another study, performed by [PERSON] et al. in 2015, documented that the peel methanolic extract possesses a potent anti-proliferative action toward several tumor cell lines as: MCF-7 (breast adenocarcinoma), A549 (lung non-small cell cancer), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma). The cytotoxicity has been investigated at different concentrations; the best antitumor effect was detected on MCF-7, with a percentage of survival inhibition amounting to 83.7% at doses of 5 mg/mL. Instead, for the other cell lines, this percentage was 77.87, 76.54, and 63.41% for PC3, A549, and SKOV3, respectively, at the same dosage used for MCF-7 [69]. Research based on the possible effect of a PE on chronic myeloid leukemia surveys that it is able to suppress cell growth by activating apoptosis and inducing cell cycle arrest. The findings of the research group led by [PERSON], outlined that the peel extract of pomegranate could inhibit K562 cell growth in a dose-dependent manner, with total cell death at the maximum concentration tested and an IC\({}_{50}\) value of 100 \(\pm\) 0.05 mg/mL. Further investigations have assessed the ability of the extract to induce the cell cycle arrest in the G2/M phase and apoptosis. Indeed, an upregulation of proapoptotic proteins caspases 9, 7, 3, and cytochrome c, and a downregulation of antiapoptotic protein Bcl-2 were detected [70]. In depth studies of genetics appraised the possible influence of PE on immunoregulatory-related miRNAs level of adipose-derived MSCs (Ad-MSCs) obtained from adipose tissue. Data suggested that the principal mechanism of action could be due to the capability to decrease the expression of PI3K\(\backslash\)AKT1\(\backslash\)NF-kB genes involved in inflammatory pathways via miRNAs expression. It plays a role in the immune modulation in Ad-MSCs. In other words, PE could possess a key role in regulating the immunomodulatory function of stem cells [71]. A new approach in the use of phytochemicals for the cancer fighting lies in the knowledge of preparing metal-based nanoparticles from the extract of different plant parts, using green synthesis procedures. Indeed, silver nanoparticles possess the capability to up- and downregulate several cellular mechanisms, and this has propelled to the forefront in investigations to use them as a possible delivery system for other chemicals or as real control systems for the cellular growth [72; 73; 74].