Department of Chemistry, Biochemistry Division, Faculty of Science, Tanta University, Tanta, Egypt.
Departement of Chemistry, College of Science, King Faisal University, Al-Ahsaa, Saudi Arabia.
Nutr Cancer. 2020;72(3):460-480. doi: 10.1080/01635581.2019.1640884. Epub 2019 Jul 18.
Egyptian propolis is a powerful antioxidant and free radical scavenger produced by bees. The current study was designed to characterize Egyptian propolis, investigate its anticancer effect in vitro and its protective role against methotrexate (MTX) toxicity in Ehrlich ascites carcinoma (EAC) experimental model. Our results revealed a high content of total phenolics, flavonoids and dihydroflavonols in propolis ethanolic extract (PEE). PEE prompted cytotoxic effects in cancer cell lines and antitumor effects against EAC mice model by reducing tumor volume, count of viable tumor cells with a significant elevation in the life span as well as the mean survival time of mice. The hepatic and renal biochemical and toxicity parameters of EAC-bearing mice treated with MTX were improved by PEE. Also, it elevates the expression of Bax, caspase-3 and cytochrome-C and reduces the Bcl expression in EAC cells. Moreover, PEE with MTX induced cell cycle arrest at the G0/G1 phase. Interestingly, the combination of PEE with MTX showed potent apoptosis as shown by DNA fragmentation gel, comet assay and dihydrofolate reductase level (DHFR). These findings demonstrate that Egyptian propolis extract had high chemical diversity and different antioxidant effects. Also, it optimizes the antitumor potential of MTX and declined its toxic effects.
埃及蜂胶是蜜蜂产生的一种具有强大抗氧化和自由基清除作用的物质。本研究旨在对埃及蜂胶进行表征，研究其在体外的抗癌作用及其在艾氏腹水癌（EAC）实验模型中对抗甲氨蝶呤（MTX）毒性的保护作用。我们的结果显示，蜂胶乙醇提取物（PEE）中总酚类、类黄酮和二氢黄酮醇的含量很高。PEE 可诱导癌细胞系产生细胞毒性作用，并对 EAC 小鼠模型产生抗肿瘤作用，减少肿瘤体积、活肿瘤细胞计数，显著提高小鼠的寿命和平均存活时间。用 PEE 处理 MTX 处理的 EAC 荷瘤小鼠的肝肾功能生化和毒性参数得到改善。此外，它还可上调 Bax、caspase-3 和细胞色素 C 的表达，降低 EAC 细胞中的 Bcl 表达。此外，PEE 联合 MTX 可诱导细胞周期停滞在 G0/G1 期。有趣的是，PEE 联合 MTX 表现出强烈的细胞凋亡，如 DNA 片段凝胶、彗星试验和二氢叶酸还原酶水平（DHFR）所示。这些发现表明，埃及蜂胶提取物具有高度的化学多样性和不同的抗氧化作用。此外，它还可以优化 MTX 的抗肿瘤潜力，并降低其毒性作用。
