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Extracts of Strawberry Fruits Induce Intrinsic Pathway of Apoptosis in Breast Cancer Cells and Inhibits Tumor Progression in Mice

机译:草莓果实提取物诱导乳腺癌细胞凋亡的内在途径并抑制小鼠肿瘤进程

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摘要

Background: The consumption of berry fruits, including strawberries, has been suggested to have beneficial effects against oxidative stress mediated diseases. Berries contain multiple phenolic compounds and secondary metabolites that contribute to their biological properties. Methodology/Principal Findings: Current study investigates the anticancer activity of the methanolic extract of strawberry (MESB) fruits in leukaemia (CEM) and breast cancer (T47D) cell lines ex vivo, and its cancer therapeutic and chemopreventive potential in mice models. Results of MTT, trypan blue and LDH assays suggested that MESB can induce cytotoxicity in cancer cells, irrespective of origin, in a concentration-and time-dependent manner. Treatment of mice bearing breast adenocarcinoma with MESB blocked the proliferation of tumor cells in a time-dependent manner and resulted in extended life span. Histological and immunohistochemical studies suggest that MESB treatment affected tumor cell proliferation by activating apoptosis and did not result in any side effects. Finally, we show that MESB can induce intrinsic pathway of apoptosis by activating p73 in breast cancer cells, when tumor suppressor gene p53 is mutated. Conclusions/Significance: The present study reveals that strawberry fruits possess both cancer preventive and therapeutic values and we discuss the mechanism by which it is achieved.
机译:背景:食用浆果,包括草莓,已被认为对氧化应激介导的疾病具有有益作用。浆果含有多种酚类化合物和次生代谢产物,有助于它们的生物学特性。方法/主要发现:当前的研究调查了草莓(MESB)果实的甲醇提取物对白血病(CEM)和乳腺癌(T47D)细胞系的体外抗癌活性,以及​​其在小鼠模型中的癌症治疗和化学预防潜力。 MTT,锥虫蓝和LDH分析的结果表明,MESB可以以浓度和时间依赖性方式诱导癌细胞的细胞毒性,无论其起源如何。用MESB处理带有乳腺腺癌的小鼠可以以时间依赖性方式阻断肿瘤细胞的增殖,从而延长了其寿命。组织学和免疫组织化学研究表明,MESB治疗可通过激活细胞凋亡来影响肿瘤细胞的增殖,并且不会导致任何副作用。最后,我们证明当抑癌基因p53发生突变时,MESB可以通过激活乳腺癌细胞中的p73来诱导细胞凋亡的内在途径。结论/意义:本研究表明草莓果实既具有预防癌症的作用,又具有治疗作用,我们讨论了它的实现机理。

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