Thiol-mediated multiple mechanisms centered on selenodiglutathione determine selenium cytotoxicity against MCF-7 cancer cells
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| 008 | 210128e20150601xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.1007/s00775-015-1254-6 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00775-015-1254-6 | ||
| 245 | 0 | 0 | |a Thiol-mediated multiple mechanisms centered on selenodiglutathione determine selenium cytotoxicity against MCF-7 cancer cells |h [Elektronische Daten] |c [Takao Tobe, Koji Ueda, Motozumi Ando, Yoshinori Okamoto, Nakao Kojima] |
| 520 | 3 | |a Selenium (Se) is an essential antioxidative micronutrient but can exert cancer-selective cytotoxicity if the nutritional levels are too high. Selenodiglutathione (GSSeSG) is a primary Se metabolite conjugated with two glutathione (GSH) moieties. GSSeSG has been suggested to be an important molecule for cytotoxicity. Here, we propose the underlying mechanisms for the potent cytotoxicity of GSSeSG: cellular intake; reductive metabolism; production of reactive oxygen species; oxidative damage to DNA; apoptosis induction. GSSeSG rather than selenite decreased cell viability and induced apoptosis accompanied by increases in intracellular Se contents. Therefore, GSSeSG-specific cytotoxicity may be ascribed to its preferable incorporation. Base oxidation and strand fragmentation in genomic DNA preceded cell death, suggesting that oxidative stress (including DNA damage) is crucial for GSSeSG cytotoxicity. Strand breaks of purified DNA were caused by the coexistence of GSSeSG and thiols (GSH, cysteine, homocysteine), but not the oxidized form or non-thiol reductants. This implies the important role of intracellular thiols in the mechanism of Se toxicity. GSH-assisted DNA strand breaks were inhibited by specific scavengers for hydrogen peroxide or hydroxyl radicals. The GSSeSG metabolite selenide induced some DNA strand breaks without GSH, whereas elemental Se did so only with GSH. These observations suggest involvement of Fenton-type reaction in the absence of transition metals and reactivation of inert elemental Se. Overall, our results suggest that chemical interactions between Se and the sulfur of thiols are crucial for the toxicity mechanisms of Se. | |
| 540 | |a SBIC, 2015 | ||
| 690 | 7 | |a Selenodiglutathione |2 nationallicence | |
| 690 | 7 | |a Cancer chemotherapy |2 nationallicence | |
| 690 | 7 | |a Glutathione |2 nationallicence | |
| 690 | 7 | |a Thiol |2 nationallicence | |
| 690 | 7 | |a Sulfur |2 nationallicence | |
| 690 | 7 | |a GSH : Glutathione |2 nationallicence | |
| 690 | 7 | |a GSSeSG : Selenodiglutathione |2 nationallicence | |
| 690 | 7 | |a GSSG : Oxidized glutathione |2 nationallicence | |
| 690 | 7 | |a HSe− : Hydrogen selenide |2 nationallicence | |
| 690 | 7 | |a H2SeO3 : Selenous acid |2 nationallicence | |
| 690 | 7 | |a ROS : Reactive oxygen species |2 nationallicence | |
| 690 | 7 | |a SSB : Single-strand break |2 nationallicence | |
| 700 | 1 | |a Tobe |D Takao |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | |
| 700 | 1 | |a Ueda |D Koji |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | |
| 700 | 1 | |a Ando |D Motozumi |u Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, 650-8586, Kobe, Japan |4 aut | |
| 700 | 1 | |a Okamoto |D Yoshinori |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | |
| 700 | 1 | |a Kojima |D Nakao |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | |
| 773 | 0 | |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/4(2015-06-01), 687-694 |x 0949-8257 |q 20:4<687 |1 2015 |2 20 |o 775 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00775-015-1254-6 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00775-015-1254-6 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tobe |D Takao |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ueda |D Koji |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ando |D Motozumi |u Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, 650-8586, Kobe, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Okamoto |D Yoshinori |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kojima |D Nakao |u Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, 468-8503, Nagoya, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/4(2015-06-01), 687-694 |x 0949-8257 |q 20:4<687 |1 2015 |2 20 |o 775 | ||