Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt.
Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt; Department of Biology, Faculty of Science, Taibah University, Saudi, Arabia.
Nutrition. 2019 Feb;58:100-109. doi: 10.1016/j.nut.2018.06.018. Epub 2018 Nov 2.
Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms.
GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated.
GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression.
The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.
通过天然膳食成分进行癌症化学预防或干预已显示出控制恶性肿瘤的巨大潜力。本研究旨在探讨葡萄籽（GSE）与葡萄皮（GSK）联合应用于接种艾氏腹水癌的小鼠的化学预防作用，并阐明其作用机制。
GSE+GSK 与标准饮食混合，在接种艾氏腹水癌细胞前 14 天开始给小鼠补充，并在整个实验过程中持续补充。监测肿瘤生长情况，评估 GSE+GSK 对肿瘤细胞的细胞周期进展和凋亡作用。
GSE+GSK 摄入可使 47%的动物预防肿瘤发生。与未用这些药物治疗的荷瘤小鼠相比，肿瘤体积和重量分别显著减少了 93.9%和 86.3%。GSE+GSK 处理导致流式细胞术评估的凋亡肿瘤细胞百分比明显增加，并通过组织病理学和电子显微镜检查得到证实。GSE+GSK 还导致肿瘤细胞的细胞周期明显停滞在 G1 期，激活 caspase-3，增加 p53 和 Bax 的表达，降低 B 细胞淋巴瘤 2 的表达和 B 细胞淋巴瘤 2：Bax 比值。此外，通过调节 p53 和 Ki67 的表达，免疫组织化学显示诱导凋亡和抑制细胞增殖。
本研究结果清楚地表明，GSE 和 GSK 的组合在艾氏腹水癌小鼠模型中代表了一种有效的化学预防和抗癌药物。这些药物作用的机制包括细胞周期停滞、诱导凋亡和抑制细胞增殖。这些发现表明，GSE+GSK 可能代表一种天然的、新颖的辅助治疗策略，用于预防实体肿瘤的生长。
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