Abd Elkarim Asmaa S, Mohamed Safaa H, Ali Naglaa A, Elsayed Ghada H, Aly Mohamed S, Elgamal Abdelbaset M, Elsayed Wael M, El-Newary Samah A
Chemistry of Tanning Materials and Leather Technology Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt.
Hormones Department, National Research Centre, 33 El-Bouhoths St., Dokki, Giza 12622, Egypt.
Int J Mol Sci. 2024 Dec 4;25(23):13024. doi: 10.3390/ijms252313024.
Lung cancer is a prevalent and very aggressive sickness that will likely claim 1.8 million lives by 2022, with an estimated 2.2 million additional cases expected worldwide. The goal of the current investigation was to determine whether petroleum ether extract of leaf could be used to treat lung cancer induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-buta-4 none (NNK) in rats. In the in vitro extract recorded, promising anticancer effects in A540 cell lines with IC were close to the reference drug, doxorubicin (14.3 and 13.8 μg/mL, respectively). A dose of 500 mg/kg/day orally for 20 weeks exhibited recovery effects on NNK-induced lung cancer with a good safety margin, where Intercellular Adhesion Molecule-1 (ICAM-1), the lung cancer biomarker, was significantly reduced by about 18.75% compared to cancer control. exhibited many anticancer mechanisms, including (i) anti-proliferation as a significant reduction in Ki67 level (20.42%), (ii) anti-angiogenesis as evident by a considerable decrease in Matrix metalloproteinase-9 (MMP-9) expression (79%), (iii) anti-inflammation as a remarked decline in Insulin-like growth factor 1 (IGF-1) expression (62%), (iv) pro-apoptotic effect as a significant activation in Forkhead box protein O1 (FOXO1) expression (262%), and (v) anti-oxidation as remarkable activation on antioxidant biomarkers either non-enzymatic or enzymatic concurrent with considerable depletion on oxidative stress biomarker, in comparison to cancer control. The histopathological examination revealed that extract showed markedly improved tissue structure and reduced pathological changes across all examined organs caused by NNK. The anti-lung cancer effect exhibited by the extract may be linked to the active ingredients of the extract that were characterized by LC-MS, such as α-linolenic acid, linoleic acid, palmitic acid, β-sitosterol, and alkaloids (berberine and magnoflorine).
肺癌是一种常见且极具侵袭性的疾病,到2022年可能会导致180万人死亡,预计全球还会新增约220万病例。当前研究的目的是确定树叶的石油醚提取物是否可用于治疗大鼠中由4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮(NNK)诱导的肺癌。在体外提取物记录中,其在A540细胞系中显示出有前景的抗癌作用,IC值接近参考药物阿霉素(分别为14.3和13.8μg/mL)。口服剂量为500mg/kg/天,持续20周,对NNK诱导的肺癌具有恢复作用,且安全边际良好,其中作为肺癌生物标志物的细胞间粘附分子-1(ICAM-1)与癌症对照组相比显著降低了约18.75%。提取物表现出许多抗癌机制,包括:(i)抗增殖,Ki67水平显著降低(20.42%);(ii)抗血管生成,基质金属蛋白酶-9(MMP-9)表达显著降低(79%);(iii)抗炎,胰岛素样生长因子1(IGF-1)表达显著下降(62%);(iv)促凋亡作用,叉头框蛋白O1(FOXO1)表达显著激活(262%);(v)抗氧化,与癌症对照组相比,非酶或酶促抗氧化生物标志物显著激活,同时氧化应激生物标志物显著消耗。组织病理学检查显示,提取物使所有检查器官的组织结构明显改善,由NNK引起的病理变化减少。提取物表现出的抗肺癌作用可能与通过液相色谱-质谱联用(LC-MS)鉴定的提取物活性成分有关,如α-亚麻酸、亚油酸、棕榈酸、β-谷甾醇以及生物碱(小檗碱和木兰碱)。