Sulforaphane potentiates RNA damage induced by different xenobiotics.
The isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage.We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in...
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2012-01-01
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doaj-d3014a57ee8f4862adf6ffc7046a042a2020-11-25T00:43:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3526710.1371/journal.pone.0035267Sulforaphane potentiates RNA damage induced by different xenobiotics.Carmela FimognariMonia LenziPiero SestiliEleonora TurriniLorenzo FerruzziPatrizia HreliaGiorgio Cantelli-FortiThe isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage.We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in different chronic diseases. Considering the ability of SFN to protect from genotoxicity, we also examined whether SFN is able to protect from RNA damage induced by different chemicals (doxorubicin, spermine, S-nitroso-N-acetylpenicillamine, H(2)O(2)). We observed that SFN was devoid of either RNA damaging and RNA protective activity in human leukemic cells. It was able to potentiate the RNA damage by doxorubicin and spermine. In the first case, the effect was attributable to its ability of modulating the bioreductive activation of doxorubicin. For spermine, the effects were mainly due to its modulation of ROS levels produced by spermine metabolism. As to the cytotoxic relevance of the RNA damage, we found that the treatment of cells with a mixture of spermine or doxorubicin plus SFN increased their proapoptotic potential. Thus it is conceivable that the presence of RNA damage might concur to the overall toxic response induced by a chemical agent in targeted cells.Since RNA is emerging as a potential target for anticancer drugs, its ability to enhance spermine- and doxorubicin-induced RNA damage and cytotoxicity could represent an additional mechanism for the potentiating effects of SFN associated with anticancer drugs.http://europepmc.org/articles/PMC3335137?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carmela Fimognari Monia Lenzi Piero Sestili Eleonora Turrini Lorenzo Ferruzzi Patrizia Hrelia Giorgio Cantelli-Forti |
spellingShingle |
Carmela Fimognari Monia Lenzi Piero Sestili Eleonora Turrini Lorenzo Ferruzzi Patrizia Hrelia Giorgio Cantelli-Forti Sulforaphane potentiates RNA damage induced by different xenobiotics. PLoS ONE |
author_facet |
Carmela Fimognari Monia Lenzi Piero Sestili Eleonora Turrini Lorenzo Ferruzzi Patrizia Hrelia Giorgio Cantelli-Forti |
author_sort |
Carmela Fimognari |
title |
Sulforaphane potentiates RNA damage induced by different xenobiotics. |
title_short |
Sulforaphane potentiates RNA damage induced by different xenobiotics. |
title_full |
Sulforaphane potentiates RNA damage induced by different xenobiotics. |
title_fullStr |
Sulforaphane potentiates RNA damage induced by different xenobiotics. |
title_full_unstemmed |
Sulforaphane potentiates RNA damage induced by different xenobiotics. |
title_sort |
sulforaphane potentiates rna damage induced by different xenobiotics. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
The isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage.We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in different chronic diseases. Considering the ability of SFN to protect from genotoxicity, we also examined whether SFN is able to protect from RNA damage induced by different chemicals (doxorubicin, spermine, S-nitroso-N-acetylpenicillamine, H(2)O(2)). We observed that SFN was devoid of either RNA damaging and RNA protective activity in human leukemic cells. It was able to potentiate the RNA damage by doxorubicin and spermine. In the first case, the effect was attributable to its ability of modulating the bioreductive activation of doxorubicin. For spermine, the effects were mainly due to its modulation of ROS levels produced by spermine metabolism. As to the cytotoxic relevance of the RNA damage, we found that the treatment of cells with a mixture of spermine or doxorubicin plus SFN increased their proapoptotic potential. Thus it is conceivable that the presence of RNA damage might concur to the overall toxic response induced by a chemical agent in targeted cells.Since RNA is emerging as a potential target for anticancer drugs, its ability to enhance spermine- and doxorubicin-induced RNA damage and cytotoxicity could represent an additional mechanism for the potentiating effects of SFN associated with anticancer drugs. |
url |
http://europepmc.org/articles/PMC3335137?pdf=render |
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