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Green Synthesized Silver Nanoparticles-Mediated Cytotoxic Effect in Colorectal Cancer Cells: NF-κB Signal Induced Apoptosis Through Autophagy

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Abstract

Green synthesized silver nanoparticles (Ag-NPs) have demonstrated promising effects, including cytotoxicity and anticancer potential, in different cell lines. Therefore, in our previous study, Ag-NPs were synthesized from the reduction of AgNO3 using Brassica rapa var. japonica (Bj) leaf extract as a reducing and stabilizing agent. The synthesized Ag-NPs were spherical in shape, with a size range of 15–30 nm. They had phase-centered cubic structure with strong growth inhibition potential against some bacteria. In continuation with our previous study, in the present study, we aimed to investigate the autophagy-regulated cytotoxic effect of Ag-NPs against human epithelial colorectal adenocarcinoma cells (Caco-2 cells). We found that the Bj leaf aqueous extract facilitated Brassica silver nanoparticles (Brassica Ag-NPs)-induced NF-κB mediated autophagy in Caco-2 cells. Results showed that Ag-NPs reduced cell viability of Caco-2 cells by inducing oxidative stress and DNA damage. Therefore, to understand the mechanism underlying the death-promoting activity of Ag-NPs in Caco-2 cells, western blotting was performed. Western blot analysis showed decreased expression of NFκB and increased expression of IκB, which is a sign of autophagy initiation. In addition, autophagosome formation was accelerated by the activity of p53 and light chain 3 (LC3) II. In addition, inhibition of Akt and mTOR also played a pivotal role in autophagy formation. Finally, excessive expansion of autophagy promoted apoptosis, which subsequently resulted in necrosis. These findings support a novel cell death-promoting function of autophagy by Ag-NPs in Caco-2 cells.

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Acknowledgments

The authors would like to thank Ms. Miyako Komori, Prof. Kamiya, Dr. Umezawa, and Dr. Parvin Begum for providing experimental support. We would also like to express our gratitude to Nahmina Begum for her generous cooperation in the statistical analysis. We are thankful to the Riken Bioresource Center, Tsukuba Ibaraki, Japan, for the generous donation of Caco-2 cells.

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Authors and Affiliations

  1. Group of Environmental Adaptation Science, Faculty of Environmental Earth Sciences, Hokkaido University, Kita 10, Nishi 5, Kita-ku, Sapporo, 060-0810, Japan

    Mahmuda Akter & Masaaki Kurasaki

  2. Nanoscience and Technology Research Laboratory, Chemistry Division, Atomic Energy Centre, Bangladesh Atomic Energy Commission, Dhaka, 1000, Bangladesh

    A. K. M. Atique Ullah

  3. Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan

    Subrata Banik & Masaaki Kurasaki

  4. Department of Public Health and Informatics, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh

    Md. Tajuddin Sikder

  5. Research Division of Higher Education, Institute for the Advancement of Higher Education, Hokkaido University, Sapporo, 060-0817, Japan

    Toshiyuki Hosokawa

  6. Faculty of Health Sciences, Hokkaido University, Sapporo, 060-0812, Japan

    Takeshi Saito

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  1. Mahmuda Akter
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Akter, M., Atique Ullah, A.K.M., Banik, S. et al. Green Synthesized Silver Nanoparticles-Mediated Cytotoxic Effect in Colorectal Cancer Cells: NF-κB Signal Induced Apoptosis Through Autophagy. Biol Trace Elem Res 199, 3272–3286 (2021). https://doi.org/10.1007/s12011-020-02463-7

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