Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F16%3A43901847" target="_blank" >RIV/60461373:22330/16:43901847 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.spandidos-publications.com/mmr/14/5/4436" target="_blank" >https://www.spandidos-publications.com/mmr/14/5/4436</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/mmr.2016.5739" target="_blank" >10.3892/mmr.2016.5739</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells

Popis výsledku v původním jazyce

Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and anti-inflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001-100 mu mol/l)-[Cu-2(sal-D, L-glu)(2)(isoquinoline) (2)]center dot 2C(2)H(5)OH (1), [Cu(sal-5-met-L-glu)(H2O)]center dot H2O (2), [Cu(ethanol)(2)(imidazole)(4)][Cu-2(sal-D, L-glu)(2)(imidazole)(2)] (3), [Cu(sal-D, L-glu)(2-methylimidazole)] (4) on the human colon carcinoma cells HT-29, the mouse noncancerous cell line NIH-3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT-29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT-29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 mu mol/l), 2 (1, 10, 50 and 100 mu mol/l), 3 (0.01, 1, 10 and 50 mu mol/l) and 4 (0.01, 0.1, 1 and 10 mu mol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondria-dependent pathway of apoptosis in HT-29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the anti-apoptotic protein Bcl-2 were reduced and those of the pro-apoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a time-dependent elevation of cyt c levels. No cyt c was detected in HT-29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu(II) complexes have potential as novel anticancer drugs.

Název v anglickém jazyce

Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells

Popis výsledku anglicky

Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and anti-inflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001-100 mu mol/l)-[Cu-2(sal-D, L-glu)(2)(isoquinoline) (2)]center dot 2C(2)H(5)OH (1), [Cu(sal-5-met-L-glu)(H2O)]center dot H2O (2), [Cu(ethanol)(2)(imidazole)(4)][Cu-2(sal-D, L-glu)(2)(imidazole)(2)] (3), [Cu(sal-D, L-glu)(2-methylimidazole)] (4) on the human colon carcinoma cells HT-29, the mouse noncancerous cell line NIH-3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT-29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT-29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 mu mol/l), 2 (1, 10, 50 and 100 mu mol/l), 3 (0.01, 1, 10 and 50 mu mol/l) and 4 (0.01, 0.1, 1 and 10 mu mol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondria-dependent pathway of apoptosis in HT-29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the anti-apoptotic protein Bcl-2 were reduced and those of the pro-apoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a time-dependent elevation of cyt c levels. No cyt c was detected in HT-29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu(II) complexes have potential as novel anticancer drugs.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

—

Projekt

<a href="/cs/project/LO1601" target="_blank" >LO1601: Pražské vysokoškolské analytické centrum II a III - NPU 2015-2020</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Medicine Reports

ISSN

1791-2997

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GR - Řecká republika

Počet stran výsledku

9

Strana od-do

4436-4444

Kód UT WoS článku

000387241600055

EID výsledku v databázi Scopus

2-s2.0-84992388750