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2-Benzhydrylsulfinyl-N-hydroxyacetamide-Na extracted from fig as a novel cytotoxic and apoptosis inducer in SKOV-3 and AMJ-13 cell lines via P53 and caspase-8 pathway
European Food Research and Technology ( IF 3.0 ) Pub Date : 2020-05-28 , DOI: 10.1007/s00217-020-03515-x
H. N. K. Al-Salman , Eman T. Ali , Majid Jabir , Ghassan M. Sulaiman , Shaker A. S. Al-Jadaan

In this study, the fruits of both mature and air-dried figs were exposed to selective sequential extracting processes using soxhlet. Different polarity and non-polarity solvents were used to increase the yield of the isolated extracts. Methanol, ethyl acetate, chloroform, and n-hexane were used to precipitate and isolate the effective compound 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na from 11 extracts and 7 compounds extracted from the organic layer. Various spectral techniques were applied, including UV-spectroscopy, FT-IR, GC-Mass, 1H-NMR, and 13C-NMR for the detection of the precipitate. The aim of current work is to deal with the synthesis of a novel compound 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na from fig fruit and study its effect as anticancer and anti-proliferative agent against SKOV-3, and AMJ-13 cells. The effect of the active compound on breast cancer cells, ovarian cancer cell proliferation was measured by the MTT assay, while its ability to induce apoptosis was detected using DAPI, acridine orange/ethidium bromide (AO/EtBr) staining, flow cytometry assay and finally mitochondrial membrane potential (MMP). Real-Time PCR was used to detect changes in the expression of mRNA for Bax and Bcl-2, P53, caspase-8, and caspase-9. Treated cancer cells with 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na significantly increased ROS synthesis, with subsequent reduction of the MMP through mechanisms that included Bax upregulation P53, Caspase-8, and Caspase-9 and Bcl-2 downregulation. The outcomes of the current study show that 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na extracted from fig fruit suppressed cancers cells’ proliferation, resulting in apoptosis as a novel pathway that involves mitochondrial mechanism via activated P53 and caspase-8 signaling. In addition, the extract exerted no toxic effects, neither on serum levels of liver functional enzymes nor on the normal histological architecture of the lungs and spleen. We demonstrated how the 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na affects cancer cells along with a study the possible mechanisms involved in this effect which is mitochondrial damage and P53 pathway. We conclude that 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na holds a promising potential as an anticancer therapeutic agent.

中文翻译:

从无花果中提取的2-苯甲基亚磺酰基-N-羟基乙酰胺-Na通过P53和caspase-8途径作为SKOV-3和AMJ-13细胞系的新型细胞毒性和凋亡诱导剂

在这项研究中,成熟的无花果和风干无花果的果实均采用索氏提取法进行选择性的顺序提取。使用不同极性和非极性溶剂可提高分离出的提取物的收率。甲醇,乙酸乙酯,氯仿和Ñ正己烷被用来沉淀和分离有效化合物2- benzhydrylsulfinyl正羟基乙酰胺钠从11只提取和从有机层萃取7种化合物。应用了各种光谱技术,包括紫外光谱,FT-IR,GC-Mass,1 H-NMR和13 C-NMR来检测沉淀物。当前工作的目的是处理新型化合物2-苯甲基亚磺酰基-n-羟基乙酰胺-Na的合成从无花果果实中提取,并研究其作为抗癌和抗增殖剂对SKOV-3和AMJ-13细胞的作用。通过MTT测定法测定活性化合物对乳腺癌细胞,卵巢癌细胞增殖的影响,同时用DAPI,a啶橙/溴化乙锭(AO / EtBr)染色,流式细胞术测定,最后检测其诱导凋亡的能力。线粒体膜电位(MMP)。实时荧光定量PCR用于检测Bax和Bcl-2,P53,caspase-8和caspase-9 mRNA的表达变化。用2-苯甲基亚磺酰基-n-羟基乙酰胺-Na处理的癌细胞显着增加ROS合成,随后通过包括Bax上调P 53在内的机制降低MMP,Caspase-8,Caspase-9和Bcl-2下调。本研究的结果表明,从无花果果实中提取的2-苯甲基亚磺酰基-n-羟基乙酰胺-Na抑制癌细胞的增殖,从而导致细胞凋亡,这是一种通过激活的P53和caspase-8信号传导参与线粒体机制的新途径。此外,该提取物对肝功能酶的血清水平和肺及脾的正常组织学结构均无毒性作用。我们证明了2-苯甲基亚磺酰基-n-羟基乙酰胺-Na如何影响癌细胞,并研究了参与这种效应的可能机制,即线粒体损伤和P 53途径。我们得出结论2-苯甲基亚磺酰基-n-羟基乙酰胺-Na作为抗癌治疗剂具有广阔的前景。
更新日期:2020-05-28
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