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葡萄皮和葡萄籽金纳米颗粒在实验动物中表现出化学预防潜力、抗氧化活性,并通过下调突变型p53、Bcl-2和全细胞角蛋白诱导细胞凋亡。

Vitis vinifera peel and seed gold nanoparticles exhibit chemopreventive potential, antioxidant activity and induce apoptosis through mutant p53, Bcl-2 and pan cytokeratin down-regulation in experimental animals.

作者信息

Nirmala J Grace, Narendhirakannan R T

机构信息

Department of Biotechnology, School of Biotechnology and Health Sciences, Karunya University (Karunya Institute of Technology and Sciences), Karunya Nagar, Coimbatore 641 114, Tamil Nadu, India.

Department of Biotechnology, School of Biotechnology and Health Sciences, Karunya University (Karunya Institute of Technology and Sciences), Karunya Nagar, Coimbatore 641 114, Tamil Nadu, India.

出版信息

Biomed Pharmacother. 2017 May;89:902-917. doi: 10.1016/j.biopha.2017.02.049. Epub 2017 Mar 8.

DOI:10.1016/j.biopha.2017.02.049
PMID:28292018
Abstract

Several studies suggest surface modifications of gold nanoparticles (AuNPs) by capping agents or surface coatings could play an important role in biological systems, and site directed delivery. The present study was carried out to assess the antioxidant and apoptotic activities of the Vitis vinifera peel and seed gold nanoparticles in experimentally induced cancer in Swiss albino mice. 12-dimethylbenz [a] anthracene (DMBA) (single application) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (thrice a week) were applied on the dorsal area of the skin to induce skin papillomagenesis in Swiss albino mice for 16 weeks. Gold nanoparticles were synthesized using Vitis vinifera peel and seed aqueous extracts and characterized by Transmission electron microscopic (TEM) analyses. On topical application, peel and seed gold nanoparticles demonstrated chemopreventive potential by significantly (p<0.05) reducing the cumulative number of tumors while increasing the antioxidant enzyme activities in the gold nanoparticles treated mice. The down-regulated expression of mutant p53, Bcl-2 and the levels of pan-cytokeratins might have facilitated the process of apoptosis in the chemical carcinogenesis process. The results were supported by the histopathological evaluation which exhibited mild dysplasia and acanthosis in the skin tissues of Vitis vinifera peel and seed AuNPs treated mice. Based on the present study, the chemopreventive action of Vitis vinifera peel and seed AuNPs is probably due to its ability to stimulate the antioxidant enzymes within the cells and suppressed abnormal skin cell proliferation that occurred during DMBA-induced skin papillomagenesis.

摘要

多项研究表明,通过封端剂或表面涂层对金纳米颗粒(AuNPs)进行表面修饰,可能在生物系统和定点递送中发挥重要作用。本研究旨在评估葡萄皮和葡萄籽金纳米颗粒对瑞士白化小鼠实验性诱导癌症的抗氧化和凋亡活性。将12-二甲基苯并[a]蒽(DMBA)(单次应用)和12-O-十四烷酰佛波醇-13-乙酸酯(TPA)(每周三次)涂抹于瑞士白化小鼠背部皮肤区域,诱导皮肤乳头状瘤形成,持续16周。使用葡萄皮和葡萄籽水提取物合成金纳米颗粒,并通过透射电子显微镜(TEM)分析进行表征。局部应用时,葡萄皮和葡萄籽金纳米颗粒通过显著(p<0.05)减少肿瘤累积数量,同时增加金纳米颗粒处理小鼠体内的抗氧化酶活性,显示出化学预防潜力。突变型p53、Bcl-2的表达下调以及全细胞角蛋白水平的降低,可能促进了化学致癌过程中的凋亡进程。组织病理学评估结果支持了这一结果,该评估显示葡萄皮和葡萄籽金纳米颗粒处理小鼠的皮肤组织出现轻度发育异常和棘皮症。基于本研究,葡萄皮和葡萄籽金纳米颗粒的化学预防作用可能归因于其刺激细胞内抗氧化酶的能力,以及抑制DMBA诱导的皮肤乳头状瘤形成过程中发生的异常皮肤细胞增殖的能力。

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