2. Academic Validation
  3. The selective cytotoxicity of silver thiosulfate, a silver complex, on MCF-7 breast cancer cells through ROS-induced cell death

The selective cytotoxicity of silver thiosulfate, a silver complex, on MCF-7 breast cancer cells through ROS-induced cell death

  • Pharmacol Rep. 2021 Jun;73(3):847-857. doi: 10.1007/s43440-021-00260-0.
Akira Ota 1,  Masataka Tajima 2,  Kazunori Mori 3,  Erika Sugiyama 2,  Vilasinee Hirunpanich Sato 4,  Hitoshi Sato 2
Affiliations

Affiliations

  • 1 Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. a.ota0810@cmed.showa-u.ac.jp.
  • 2 Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
  • 3 Division of Cancer Cell Biology, Department of Pharmaceutical Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
  • 4 Department of Pharmacology, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand.
PMID: 33864630 DOI: 10.1007/s43440-021-00260-0
Abstract

Background: Silver is a transition metal that is known to be less toxic than platinum. However, only few studies have reported the Anticancer effects of some silver complexes and their possibility as an alternative to platinum complex. This study investigated the Anticancer effects of the silver thiosulfate complex (STS), [Ag(S2O3)2]3-, consisting of silver and sodium thiosulfate.

Methods: In vitro cytotoxic activity of STS was investigated comparatively in human Cancer cell lines (K562 and MCF-7) and normal human cells (mesenchymal stem cells and mammary epithelial cells). For its Anticancer effects, cell cycle, mode of cell death, morphological changes, and accumulation of intracellular ROS and GSH were evaluated in MCF-7 to provide mechanistic insights.

Results: STS showed a concentration-dependent cytotoxicity in MCF-7 cell, which was abolished by pretreatment with N-acetylcysteine, suggesting ROS accumulation by STS. Moreover, STS caused cell cycle arrest at the G1 phase, decrease in the GSH levels, and morphological changes in MCF-7. Direct measurement of ROS demonstrated the elevation of intracellular ROS accumulation in Cancer cells treated with STS; however, neither cytotoxicity nor ROS accumulation was observed in normal human cells.

Conclusion: The results obtained here are the first evidence to show that STS exhibited an Anticancer activity through ROS-induced mechanisms, and that its cytotoxicity is highly selective to Cancer cells. The results of the present study warrant further investigation on the detailed mechanism of STS actions, as well as its in vivo effectiveness and safety for clinical application.

Keywords

Anticancer effects; Cancer cell selectivity; MCF-7 breast cancer cells; Reactive oxygen species (ROS); Silver thiosulfate; Silver(I) complexes.

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