Apple pectin: A natural source for cancer suppression in 4T1 breast cancer cells in vitro and express p53 in mouse bearing 4T1 cancer tumors, in vivo

Apple pectin: A natural source for cancer suppression in 4T1 breast cancer cells in vitro and express p53 in mouse bearing 4T1 cancer tumors, in vivo
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DOI:
10.1016/j.biopha.2016.09.080
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发表时间:
2016-12-01
影响因子:
7.5
通讯作者:
Sepehri, Houri
Sepehri, Houri
中科院分区:
医学2区
文献类型:
--
作者:
Delphi, Ladan;Sepehri, Houri

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目的:癌症相关死亡人数的增加使得研究开发新的药物和治疗方法变得至关重要。开发新疗法的主要目的之一是利用具有诱导细胞凋亡能力的自然资源。果胶是一种天然化合物,是一种在苹果中发现的具有抗癌特性的复杂多糖。本研究的目的是研究果胶酸在体外对4T1乳腺癌细胞和体内乳腺癌动物模型的抗癌特性。实验设计:采用MTT细胞增殖法、双荧光染色法(吖啶橙/溴化乙啶)和细胞周期法检测体外细胞凋亡。将4T1细胞植入雌性BALB/c小鼠体内进行体内研究。采用肿瘤体积、组织学分析、P53免疫组化染色及隧道试验评价肿瘤细胞凋亡。结果:体外实验结果显示,0.1%浓度的果胶酸可诱导细胞凋亡,抑制细胞生长(p < 0.001),减少细胞附着、染色质碎片化、膜起泡,阻断亚g1期(p < 0.001)。此外,体内研究表明,果胶酸可以通过过表达P53,增加凋亡细胞的数量来抑制肿瘤的进展。结论:果胶酸作为苹果的一种天然成分,具有抑制癌细胞和原发肿瘤转移的作用。这种潜在的作用主要是由于其诱导细胞凋亡的能力。(C) 2016 Elsevier Masson SAS。版权所有。
Purpose: Increase in the number of cancer related deaths has made the study on developing new drugs and treatments essential. One of the main aims in developing new therapies is to use natural resources which have the ability to induce apoptosis. Pectin is one of these natural compounds, a complex polysaccharide found in apples with anti-cancer properties. The aim of this study was to examine anticancer properties of pectic acid both in vitro in 4T1 breast cancer cells and in vivo using an animal model of breast cancer.Experimental design: MTT cell proliferation assays, double fluorescence staining (acridine orange/ethidium bromide) and cell cycle analysis were employed to measure apoptosis in vitro. 4T1 cells were implanted into female BALB/c mice for in vivo studies. Then tumor volumes, histological analysis and immunohistochemical staining of P53 and tunnel test were applied to evaluate apoptosis in tumors.Results: The results of in vitro studies showed that concentration of 0.1% of pectic acid could induce apoptosis, inhibit cell growth (p < 0.001) and reduce cell attachment, fragmented chromatin, and membrane blebbing as well as blocking the sub-G1 phase (p < 0.001). In addition, in vivo studies showed that pectic acid could inhibit the progression of tumors through over-expression of P53 and increasing the number of apoptotic cells.Conclusion: Our results demonstrated that pectic acid, a natural component of apple, can prevent metastasis in both cancer cell lines and primary tumors. This potential effect is mainly due to its ability to induce apoptosis. (C) 2016 Elsevier Masson SAS. All rights reserved.