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3-Acetyl-bis(2-chloro-4-nitrophenyl) triazene is a potent antitumor agent that induces oxidative stress and independently activates the stress-activated protein kinase/c-Jun NH2-terminal kinase pathway


Brozović, Anamaria; Stojanović, Nikolina; Ambriović-Ristov, Andreja; Brozović Krijan, Antonija; Polanc, Slovenko; Osmak, Maja
3-Acetyl-bis(2-chloro-4-nitrophenyl) triazene is a potent antitumor agent that induces oxidative stress and independently activates the stress-activated protein kinase/c-Jun NH2-terminal kinase pathway // Anti-cancer drugs, 25 (2014), 3; 289-295 doi:10.1097/CAD.000000000000006 (međunarodna recenzija, članak, znanstveni)


Naslov
3-Acetyl-bis(2-chloro-4-nitrophenyl) triazene is a potent antitumor agent that induces oxidative stress and independently activates the stress-activated protein kinase/c-Jun NH2-terminal kinase pathway
(3-Acetyl-bis(2-chloro-4-nitrophenyl) triazene is a potent antitumor agent that induces oxidative stress and independently activates the stress-activated protein)

Autori
Brozović, Anamaria ; Stojanović, Nikolina ; Ambriović-Ristov, Andreja ; Brozović Krijan, Antonija ; Polanc, Slovenko ; Osmak, Maja

Izvornik
Anti-cancer drugs (0959-4973) 25 (2014), 3; 289-295

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Anticancer drugs ; diaryltriazene ; endoplasmic reticulum stress ; reactive oxygen species ; SAPK/JNK

Sažetak
Previously, we described the synthesis and biological activity of a new class of anticancer molecules that preferentially target malignant cells and may serve as potential antitumor agents. Among several synthesized agents, we selected 3-acetyl-1, 3-bis(2-chloro-4- nitrophenyl)-1-triazene (8b) as a representative of the group of 4-nitro-substituted 1, 3-diaryltriazenes. The aim of this study was to further investigate the mechanism of cell response to the 8b compound. The HeLa human cervical carcinoma cell line was used as an experimental model to further investigate the mechanism of cell response to the 8b compound. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) colorimetric assay was used to address cell survival, and western blot (immunoblotting) was used for the expression of relevant proteins after 8b drug exposure. The pretreatment of HeLa cells with salubrinal, a specific inhibitor of endoplasmic reticulum (ER) stress, confirmed the importance of ER stress in apoptosis induced by 8b. We also demonstrate that 8b triggers the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) in a timedependent and dose-dependent manner. Moreover, the inhibition of SAPK/JNK activity by JNK II before 8b treatment increased the survival rate of HeLa cells relative to survival in the presence of 8b alone, indicating the importance of this kinase in cell death. The simultaneous inhibition of ER stress induction and SAPK/JNK activation increased the survival of HeLa cells upon 8b treatment more than inhibition of both pathways independently, suggesting the separate triggering of both signaling pathways. Our data indicate that cytotoxic activity of the novel compound 8b is based on its ability to induce ER stress and SAPK/JNK signaling pathways independently, driving cells to cell death.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
098-0982913-2748 - Stanični odgovor na citotoksične spojeve i razvoj otpornosti (Maja Osmak, )
098-0982913-2850 - Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike (Andreja Ambriović Ristov, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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