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Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells

Samo za registrovane korisnike
2016
Autori
Srdić-Rajić, Tatjana
Nikolic, Katarina
Cavic, Milena
Đokić, Ivana
Gemović, Branislava S.
Perović, Vladimir R.
Veljković, Nevena V.
Članak u časopisu
Metapodaci
Prikaz svih podataka o dokumentu
Apstrakt
Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signal...ing in hematologic malignancies and to search for medicinally active agents. (C) 2015 Elsevier B.V. All rights reserved.

Ključne reči:
Rilmenidine / Imidazoline I1 receptor signaling / Apoptosis / Proliferation / K562 / DNA damage
Izvor:
European Journal of Pharmaceutical Sciences, 2016, 81, 172-180
Projekti:
  • Primena EIIP/ISM bioinformatičke platforme u otkrivanju novih terapeutskih targeta i potencijalnih terapeutskih molekula (RS-173001)
  • Farmakodinamska i farmakogenomska ispitivanja novijih lekova u lečenju solidnih tumora (RS-41026)

DOI: 10.1016/j.ejps.2015.10.017

ISSN: 0928-0987; 1879-0720

PubMed: 26598394

WoS: 000367787700021

Scopus: 2-s2.0-84946239745
[ Google Scholar ]
9
7
URI
http://vinar.vin.bg.ac.rs/handle/123456789/884
Kolekcije
  • WoS Import
Institucija
Vinča
TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Nikolic, Katarina
AU  - Cavic, Milena
AU  - Đokić, Ivana
AU  - Gemović, Branislava S.
AU  - Perović, Vladimir R.
AU  - Veljković, Nevena V.
PY  - 2016
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/884
AB  - Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents. (C) 2015 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmaceutical Sciences
T1  - Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells
VL  - 81
SP  - 172
EP  - 180
DO  - 10.1016/j.ejps.2015.10.017
ER  - 
@article{
author = "Srdić-Rajić, Tatjana and Nikolic, Katarina and Cavic, Milena and Đokić, Ivana and Gemović, Branislava S. and Perović, Vladimir R. and Veljković, Nevena V.",
year = "2016",
url = "http://vinar.vin.bg.ac.rs/handle/123456789/884",
abstract = "Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents. (C) 2015 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells",
volume = "81",
pages = "172-180",
doi = "10.1016/j.ejps.2015.10.017"
}
Srdić-Rajić T, Nikolic K, Cavic M, Đokić I, Gemović BS, Perović VR, Veljković NV. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. European Journal of Pharmaceutical Sciences. 2016;81:172-180
Srdić-Rajić, T., Nikolic, K., Cavic, M., Đokić, I., Gemović, B. S., Perović, V. R.,& Veljković, N. V. (2016). Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells.
European Journal of Pharmaceutical Sciences, 81, 172-180.
https://doi.org/10.1016/j.ejps.2015.10.017
Srdić-Rajić Tatjana, Nikolic Katarina, Cavic Milena, Đokić Ivana, Gemović Branislava S., Perović Vladimir R., Veljković Nevena V., "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells" 81 (2016):172-180,
https://doi.org/10.1016/j.ejps.2015.10.017 .

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