由于其丰富的可水解花青素和单宁，石榴皮和籽可食用，并具有强大的抗氧化和抗炎特性。本研究旨在追踪石榴籽和皮乙醇提取物对肝癌细胞系（即HepG2）的抗癌活性，以及相关的组织病理学、免疫组织化学、遗传和氧化应激状况。体外研究表明，两种提取物均以酚类、多酚类和酸为主，并具有抗肝癌细胞系（HepG2）的抗增殖潜力，其中种子的50％抑制浓度（IC50）显著降低了皮的IC50。试验提取物的毒性与浓度相关，并伴随细胞周期在G0/G1和S期阻滞和细胞死亡，但不在G2/M期阻滞。细胞阻滞伴随着ROS、MDA的升高和SOD、GSH和Catalase的降低。凋亡相关基因显示出明显的上调，包括凋亡促进基因（P53）、Cy-C、Bax和casp-3和下调抗凋亡基因（Bcl-2）。此外，在试验提取物的作用下固相-3和P53蛋白质得到大量表达。组织病理学研究表明，未处理的细胞（对照组）为正常细胞，有核仁多形性和高染色质核，而种子和皮提取物处理的细胞显示出坏死，混合着染色质，核内嗜酸性物质，破裂细胞膜，以及核膜和不规则细胞的萎缩凋亡细胞。最后，免疫组织化学检测到的PCNA基因在种子提取物处理下显著下调，而在用皮提取物处理细胞的情况下则未见效应。© 2023 Nasr et al.

Owing to their great quantity of hydrolyzable anthocyanins and tannins, the peel and seeds of pomegranate are edible and possess potent anti-oxidant and anti-inflammatory characteristics. This work aims to trace the pomegranate seed and peel ethanolic extracts' anticancer activity against liver cancer cell line, namely HepG2 and related histopathological, immunohistochemical, genetic and oxidative stress profile.In vitro study for both seed and peel extract showed the prevalence of phenols, polyphenols and acids, those have anti-proliferative potential against liver cancer cell line (HepG2) with 50% inhibitory concentration (IC50) of seed significantly reduced that of peel. Toxicity of test extracts was concentration dependent and accompanied with cell cycle arrest and cell death at theG0/G1 and S phases but not at the G2/M phase. Cell arrest was supplemented with raised ROS, MDA and decreased SOD, GSH and Catalase.Apoptosis-related genes showed significant up-expression of pro-apoptotic gene (P53), Cy-C, Bax, and casp-3 and down expression of anti-apoptotic gene (Bcl-2). Also, Casp-3 and P53 proteins were substantially expressed under the effect of test extracts. Histopathological study demonstrated that the untreated cells (control group) were regular cells with nuclear pleomorphism and hyperchromatic nuclei, while seed and peel extracts-treated cells showed necrosis, mixed euchromatin and heterochromatin, intra-nuclear eosinophilic structures, burst cell membranes, and the shrunken apoptotic cells with nuclear membranes and irregular cells. Finally, PCNA gene detected by immunohistochemistry was down regulated significantly under the effect of seed extract treatment than in case of cell medication with peel extract.© 2023 Nasr et al.