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In vivo antitumor activity of by-products of Passiflora edulis f. flavicarpa Deg. Rich in medium and long chain fatty acids evaluated through oxidative stress markers, cell cycle arrest and apoptosis induction
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-06-07 , DOI: 10.1016/j.fct.2018.06.010
Nádia S.R.S. Mota , Maicon R. Kviecinski , Rodrigo C. Zeferino , Daniela A. de Oliveira , Lizandra C. Bretanha , Sandra R.S. Ferreira , Gustavo A. Micke , Danilo Wilhelm Filho , Rozangela C. Pedrosa , Fabiana Ourique

Antiinflammatory and antitumor activity has been reported in Passiflora edulis (yellow passion fruit) nevertheless the intrinsic mechanisms of action are not fully elucidated. The present study aimeds to perform a comparison between the antitumor activity involving the crude extract (HCE) and the supercritical fluid extract with ethanol as co-solvent (SFEtOH) from P. edulis f. flavicarpa Deg. The in vitro cytotoxicity was evaluated in MCF-7 cells, while the in vivo antitumor activity was assessed in male Balb/c mice inoculated with Ehrlich carcinoma cells. SFEtOH exhibited higher antitumor activity compared to HCE. Wherein, SFEtOH showed an EC50 of 264.6 μg/mL against MCF-7 cells as well as an increased inhibition of tumor growth of 48.5% (p < 0.001) in male Balb/c mice, thereby promoting an increased mice lifespan to approximately 42%. Moreover, SFEtOH caused lipid (p < 0.001) and protein (p < 0.001) oxidation by increasing glutathione redox cycle activity while decreased the thioredoxin reductase activity (p < 0.001). SFEtOH also induced oxidative DNA damage in Ehrlich ascites carcinoma (EAC) cells leading to G2/M cycle arrest and has increased apoptotic cells up to 48.2%. These data suggest that the probable mechanisms of antitumor effect are associated to the lipid, protein and DNA damage, leading to cell cycle arrest and triggering apoptosis via mitochondrial pathway, should be probable due to the presence of medium and long chain fatty acids such as lauric acid.



中文翻译:

西番莲副产物的体内抗肿瘤活性。黄皮果。通过氧化应激标记,细胞周期停滞和凋亡诱导评估富含中和长链脂肪酸

西番莲(黄色西番莲)中已报道了抗炎和抗肿瘤活性,但尚未充分阐明其内在作用机理。本研究旨在对涉及粗提物(HCE)和超临界流体提取物的抗肿瘤活性进行比较,其中乙醇作为共溶剂(SFEtOH)来自可食假单胞菌(P. edulis f。)。黄皮果。在体外细胞毒性在MCF-7细胞进行评价,而在体内的抗肿瘤活性在用Ehrlich肿瘤细胞接种的雄性Balb / c小鼠评估。与HCE相比,SFEtOH表现出更高的抗肿瘤活性。其中SFEtOH的EC 50在男性Balb / c小鼠中,对MCF-7细胞的免疫抑制率为264.6μg/ mL,对肿瘤生长的抑制作用增加了48.5%(p <0.001),从而将小鼠的寿命提高了约42%。此外,SFEtOH通过增加谷胱甘肽氧化还原循环活性而引起脂质(p <0.001)和蛋白质(p <0.001)氧化,同时降低了硫氧还蛋白还原酶活性(p <0.001)。SFEtOH还可以诱导Ehrlich腹水癌(EAC)细胞中的DNA氧化损伤,从而导致G2 / M周期停滞,并且使凋亡细胞增加高达48.2%。这些数据表明,抗肿瘤作用的可能机制与脂质,蛋白质和DNA损伤有关,导致细胞周期停滞并通过线粒体途径触发凋亡,这可能是由于存在中长链脂肪酸(如月桂酸)而引起的。酸。

更新日期:2018-06-07
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