J 2016

Sulforaphane-induced apoptosis involves the type 1 IP3 receptor

HUDECOVA, Sona, Jana MARKOVA, Veronika SIMKO, Lucia CSADEROVA, Tibor STRAČINA et. al.

Základní údaje

Originální název

Sulforaphane-induced apoptosis involves the type 1 IP3 receptor

Autoři

HUDECOVA, Sona (703 Slovensko), Jana MARKOVA (703 Slovensko), Veronika SIMKO (703 Slovensko), Lucia CSADEROVA (703 Slovensko), Tibor STRAČINA (703 Slovensko, domácí), Marta SIROVA (703 Slovensko), Michaela FOJTŮ (203 Česká republika, domácí), Eliska SVASTOVA (703 Slovensko), Paulina GRONESOVA (703 Slovensko), Michal PASTOREK (703 Slovensko), Marie NOVÁKOVÁ (203 Česká republika, garant, domácí), Dana CHOLUJOVA (703 Slovensko), Juraj KOPACEK (703 Slovensko), Silvia PASTOREKOVA (703 Slovensko), Jan SEDLAK (703 Slovensko) a Olga KRIZANOVA (703 Slovensko)

Vydání

Oncotarget, Albany, Impact Journals LLC, 2016, 1949-2553

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.168

Kód RIV

RIV/00216224:14110/16:00091552

Organizační jednotka

Lékařská fakulta

UT WoS

000387164700045

Klíčová slova anglicky

type 1 IP3 receptor; sulforaphane; apoptosis. NRF2; nude mice

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 10. 1. 2017 10:54, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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.