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

Abstract

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.

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Acknowledgements

The authors are warmly grateful to all those working in analytical research laboratories who have made a lot of effort to achieve the results of this research. The authors report that this work was supported by the laboratories of the Department of Chemistry, University of Sheffield, UK. College of the Pharmacy, University of Basrah, Basrah, Iraq and Department of Applied Sciences, University of Technology, Baghdad, Iraq.

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Correspondence to Majid Jabir.

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All Institutional and National Guidelines for the care and use of animals were followed and approved by Animal Care and Ethics Committee at Biotechnology Division, Applied Sciences Department, University of Technology, Baghdad, Iraq according to Ref. No. AS 569/12/01/2019.

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Al-Salman, H.N.K., Ali, E.T., Jabir, M. et al. 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. Eur Food Res Technol 246, 1591–1608 (2020). https://doi.org/10.1007/s00217-020-03515-x

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Keywords

  • 2-Benzhydrylsulfinyl-n-hydroxyacetamide-Na
  • Anticancer activity
  • P53
  • Caspase-8