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Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells

Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decompositio...

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Autores principales: Tsuma-Kaneko, Mitsuyo, Sawanobori, Masakazu, Kawakami, Shohei, Uno, Tomoko, Nakamura, Yoshihiko, Onizuka, Makoto, Ando, Kiyoshi, Kawada, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255900/
https://www.ncbi.nlm.nih.gov/pubmed/30478296
http://dx.doi.org/10.1038/s41598-018-35730-8
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author Tsuma-Kaneko, Mitsuyo
Sawanobori, Masakazu
Kawakami, Shohei
Uno, Tomoko
Nakamura, Yoshihiko
Onizuka, Makoto
Ando, Kiyoshi
Kawada, Hiroshi
author_facet Tsuma-Kaneko, Mitsuyo
Sawanobori, Masakazu
Kawakami, Shohei
Uno, Tomoko
Nakamura, Yoshihiko
Onizuka, Makoto
Ando, Kiyoshi
Kawada, Hiroshi
author_sort Tsuma-Kaneko, Mitsuyo
collection PubMed
description Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (H(2)O(2)) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of H(2)O(2) and abrogating the apoptosis pathways induced by VC. In vivo, in the presence of EEI, the growth inhibitory effect of VC on K562 cells was completely abrogated; in fact, VC enhanced K562 cell growth. Reduction of EEI restored the apoptosis-inducing effect of VC in vitro and enhanced the growth inhibitory effect of VC in vivo. Further studies are warranted to investigate whether the combination of VC and iron depletion has similar effects in various other leukemic or cancer cells against which VC has been effective in previous experimental studies.
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spelling pubmed-62559002018-12-03 Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells Tsuma-Kaneko, Mitsuyo Sawanobori, Masakazu Kawakami, Shohei Uno, Tomoko Nakamura, Yoshihiko Onizuka, Makoto Ando, Kiyoshi Kawada, Hiroshi Sci Rep Article Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (H(2)O(2)) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of H(2)O(2) and abrogating the apoptosis pathways induced by VC. In vivo, in the presence of EEI, the growth inhibitory effect of VC on K562 cells was completely abrogated; in fact, VC enhanced K562 cell growth. Reduction of EEI restored the apoptosis-inducing effect of VC in vitro and enhanced the growth inhibitory effect of VC in vivo. Further studies are warranted to investigate whether the combination of VC and iron depletion has similar effects in various other leukemic or cancer cells against which VC has been effective in previous experimental studies. Nature Publishing Group UK 2018-11-26 /pmc/articles/PMC6255900/ /pubmed/30478296 http://dx.doi.org/10.1038/s41598-018-35730-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tsuma-Kaneko, Mitsuyo
Sawanobori, Masakazu
Kawakami, Shohei
Uno, Tomoko
Nakamura, Yoshihiko
Onizuka, Makoto
Ando, Kiyoshi
Kawada, Hiroshi
Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title_full Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title_fullStr Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title_full_unstemmed Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title_short Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells
title_sort iron removal enhances vitamin c-induced apoptosis and growth inhibition of k-562 leukemic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255900/
https://www.ncbi.nlm.nih.gov/pubmed/30478296
http://dx.doi.org/10.1038/s41598-018-35730-8
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