Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Nutr Cancer. 2022;74(1):250-264. doi: 10.1080/01635581.2020.1871496. Epub 2021 Jan 13.
The aim of the present study was to investigate the anti-tumor effect of sesamol (SML), a nutritional phenolic compound of sesame, in solid Ehrlich carcinoma (SEC) model in mice and its ability to enhance doxorubicin (DOX) anti-tumor activity. Moreover, we analyzed the ability of SML to protect against DOX-induced cardiotoxicity.
SML (70 mg/kg), DOX (2 mg/kg) and their combination were given to mice bearing SEC for 21 day. The mRNA level of Fas, FasL, TRAILR2, TRAIL, caspase-3 and Bcl-2 were assessed by qPCR. Tumor and cardiac tissues were examined for histopathological changes by hematoxylin and eosin. Active caspase-3 was scored by immunohistochemical analysis.
SML treatment significantly decreased solid tumor size and weight. In addition, SML enhanced DOX anti-tumor activity. SML treatment either alone or in combination with DOX induced upregulation of Fas/FasL and TRAILR2/TRAIL gene expression. Moreover, SML increased caspase-3 protein and gene expressions and decreased Bcl-2 gene expression.
SML upregulates death receptors expression and enhances apoptosis induction in tumor cells that may explain its anti-tumor activity. Not only that, but SML also enhances DOX anti-tumor activity and attenuates its cardiotoxicity.
本研究旨在探讨芝麻酚（SML）——芝麻中的一种营养性酚类化合物，对小鼠实体艾氏腹水癌（SEC）模型的抗肿瘤作用及其增强阿霉素（DOX）抗肿瘤活性的能力。此外，我们分析了 SML 对抗 DOX 诱导的心脏毒性的能力。
给予荷 SEC 小鼠 SML（70mg/kg）、DOX（2mg/kg）及其组合 21 天。通过 qPCR 评估 Fas、FasL、TRAILR2、TRAIL、caspase-3 和 Bcl-2 的 mRNA 水平。通过苏木精和伊红染色检查肿瘤和心脏组织的组织病理学变化。通过免疫组织化学分析对活性 caspase-3 进行评分。
SML 治疗可显著减小实体瘤的大小和重量。此外，SML 增强了 DOX 的抗肿瘤活性。SML 单独或与 DOX 联合治疗可诱导 Fas/FasL 和 TRAILR2/TRAIL 基因表达上调。此外，SML 增加了 caspase-3 蛋白和基因表达，并降低了 Bcl-2 基因表达。
SML 上调了死亡受体的表达，并增强了肿瘤细胞的凋亡诱导，这可能解释了其抗肿瘤活性。不仅如此，SML 还增强了 DOX 的抗肿瘤活性，并减轻了其心脏毒性。
