Jabbar Ahmed Aj, Ibrahim Ibrahim Abdel Aziz, Abdullah Fuad O, Aziz Kareem Fattah, Alzahrani Abdullah R, Abdulla Mahmood Ameen
Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil 44001, Iraq.
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi Arabia.
Curr Issues Mol Biol. 2023 Jan 18;45(2):885-902. doi: 10.3390/cimb45020057.
species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.
紫草科植物因其广泛的药用潜力而闻名于世,是著名的药用植物。本研究旨在探讨提取物(OME)对大鼠由氧化偶氮甲烷(AOM)诱导的异常隐窝灶(ACF)的抗癌(体外)和化学保护(体内)功效。通过MTT法测定OME对两种人类肿瘤细胞系(Caco-2和HT-29)的体外抗增殖作用。通过对白化大鼠血清和组织匀浆进行各种生化分析,并测定氧化应激生物标志物,研究OME的体内化学保护作用。测定结肠的炎症生物标志物、结肠大体形态(用亚甲蓝)、ACF形成以及结肠组织病理学(苏木精和伊红染色)。还通过Bax和Bcl-2蛋白表达评估结肠组织的免疫组织化学。结果表明,OME对Caco-2和HT-29结肠癌细胞的抗肿瘤活性范围为22.28 - 36.55 µg/mL。补充OME导致ACF值显著下降,并改善了大鼠的免疫组织化学,表现为Bax上调和Bcl-2蛋白表达下调。这些结果表明,OME可能对AOM诱导的结肠癌具有化学保护作用,其表现为可能通过抑制自由基、炎症以及刺激结肠抗氧化防御系统(超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶)和Nrf2-Keap1途径的正向调节来减弱ACF的形成。