2-Benzhydrylsulfinyl-N-hydroxyacetamide-Naextracted from fig as a novel cytotoxic and apoptosis inducer in SKOV-3 and AMJ-13 cell lines via P53 and caspase-8 pathway

被引:45
作者
Al-Salman, H. N. K. [1 ]
Ali, Eman T. [2 ]
Jabir, Majid [3 ]
Sulaiman, Ghassan M. [3 ]
Al-Jadaan, Shaker A. S. [1 ]
机构
[1] Univ Basrah, Coll Pharm, Dept Pharmaceut Chem, Basrah, Iraq
[2] Univ Basrah, Coll Pharm, Dept Clin Lab Sci, Basrah, Iraq
[3] Univ Technol Baghdad, Dept Appl Sci, Div Biotechnol, Baghdad, Iraq
关键词
2-Benzhydrylsulfinyl-n-hydroxyacetamide-Na; Anticancer activity; P53; Caspase-8; FICUS-CARICA L; BREAST-CANCER; SUPPRESSES; MIGRATION; EXTRACTS; CYCLE;
D O I
10.1007/s00217-020-03515-x
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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, andn-hexane were used to precipitate and isolate the effective compound2-benzhydrylsulfinyl-n-hydroxyacetamide-Nafrom 11 extracts and 7 compounds extracted from the organic layer. Various spectral techniques were applied, including UV-spectroscopy, FT-IR, GC-Mass,H-1-NMR, and(13)C-NMR for the detection of the precipitate. The aim of current work is to deal with the synthesis of a novel compound2-benzhydrylsulfinyl-n-hydroxyacetamide-Nafrom 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 with2-benzhydrylsulfinyl-n-hydroxyacetamide-Nasignificantly increased ROS synthesis, with subsequent reduction of the MMP through mechanisms that included Bax upregulation P-53, Caspase-8, and Caspase-9 and Bcl-2 downregulation. The outcomes of the current study show that2-benzhydrylsulfinyl-n-hydroxyacetamide-Naextracted 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 the2-benzhydrylsulfinyl-n-hydroxyacetamide-Naaffects cancer cells along with a study the possible mechanisms involved in this effect which is mitochondrial damage and P(53)pathway. We conclude that2-benzhydrylsulfinyl-n-hydroxyacetamide-Naholds a promising potential as an anticancer therapeutic agent.
引用
收藏
页码:1591 / 1608
页数:18
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