| HUDECOVA, Sona, Jana MARKOVA, Veronika SIMKO, Lucia CSADEROVA, Tibor STRAČINA, Marta SIROVA, Michaela FOJTŮ, Eliska SVASTOVA, Paulina GRONESOVA, Michal PASTOREK, Marie NOVÁKOVÁ, Dana CHOLUJOVA, Juraj KOPACEK, Silvia PASTOREKOVA, Jan SEDLAK and Olga KRIZANOVA. Sulforaphane-induced apoptosis involves the type 1 IP3 receptor. Oncotarget. Albany: Impact Journals LLC, 2016, vol. 7, No 38, p. 61403-61418. ISSN 1949-2553. |
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@article{1359620,
author = {Hudecova, Sona and Markova, Jana and Simko, Veronika and Csaderova, Lucia and Stračina, Tibor and Sirova, Marta and Fojtů, Michaela and Svastova, Eliska and Gronesova, Paulina and Pastorek, Michal and Nováková, Marie and Cholujova, Dana and Kopacek, Juraj and Pastorekova, Silvia and Sedlak, Jan and Krizanova, Olga},
article_location = {Albany},
article_number = {38},
keywords = {type 1 IP3 receptor; sulforaphane; apoptosis. NRF2; nude mice},
language = {eng},
issn = {1949-2553},
journal = {Oncotarget},
title = {Sulforaphane-induced apoptosis involves the type 1 IP3 receptor},
volume = {7},
year = {2016}
}
TY - JOUR
ID - 1359620
AU - Hudecova, Sona - Markova, Jana - Simko, Veronika - Csaderova, Lucia - Stračina, Tibor - Sirova, Marta - Fojtů, Michaela - Svastova, Eliska - Gronesova, Paulina - Pastorek, Michal - Nováková, Marie - Cholujova, Dana - Kopacek, Juraj - Pastorekova, Silvia - Sedlak, Jan - Krizanova, Olga
PY - 2016
TI - Sulforaphane-induced apoptosis involves the type 1 IP3 receptor
JF - Oncotarget
VL - 7
IS - 38
SP - 61403-61418
EP - 61403-61418
PB - Impact Journals LLC
SN - 19492553
KW - type 1 IP3 receptor
KW - sulforaphane
KW - apoptosis. NRF2
KW - nude mice
N2 - In this study we show that anti-tumor effect of sulforaphane (SFN) is partially realized through the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). This effect was verified in vitro on three different stable cell lines and also in vivo on the model of nude mice with developed tumors. Early response (6 hours) of A2780 ovarian carcinoma cells to SFN treatment involves generation of mitochondrial ROS and increased transcription of NRF2 and its downstream regulated genes including heme oxygenase 1, NAD(P)H:quinine oxidoreductase 1, and KLF9. Prolonged SFN treatment (24 hours) upregulated expression of NRF2 and IP3R1. SFN induces a time-dependent phosphorylation wave of HSP27. Use of IP3R inhibitor Xestospongin C (Xest) attenuates both SFN-induced apoptosis and the level of NRF2 protein expression. In addition, Xest partially attenuates anti-tumor effect of SFN in vivo. SFN-induced apoptosis is completely inhibited by silencing of IP3R1 gene but only partially blocked by silencing of NRF2; silencing of IP3R2 and IP3R3 had no effect on these cells. Xest inhibitor does not significantly modify SFN-induced increase in the rapid activity of ARE and AP1 responsive elements. We found that Xest effectively reverses the SFN-dependent increase of nuclear content and decrease of reticular calcium content. In addition, immunofluorescent staining with IP3R1 antibody revealed that SFN treatment induces translocation of IP3R1 to the nucleus. Our results clearly show that IP3R1 is involved in SFN-induced apoptosis through the depletion of reticular calcium and modulation of transcription factors through nuclear calcium up-regulation.
ER -
HUDECOVA, Sona, Jana MARKOVA, Veronika SIMKO, Lucia CSADEROVA, Tibor STRAČINA, Marta SIROVA, Michaela FOJTŮ, Eliska SVASTOVA, Paulina GRONESOVA, Michal PASTOREK, Marie NOVÁKOVÁ, Dana CHOLUJOVA, Juraj KOPACEK, Silvia PASTOREKOVA, Jan SEDLAK and Olga KRIZANOVA. Sulforaphane-induced apoptosis involves the type 1 IP3 receptor. \textit{Oncotarget}. Albany: Impact Journals LLC, 2016, vol.~7, No~38, p.~61403-61418. ISSN~1949-2553.
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