Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells
Само за регистроване кориснике
2016
Аутори
Srdić-Rajić, TatjanaNikolić, Katarina M.
Čavić, Milena R.
Đokić, Ivana
Gemović, Branislava S.
Perović, Vladimir R.
Veljković, Nevena V.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Rilmenidine / Imidazoline I1 receptor signaling / Apoptosis / Proliferation / K562 / DNA damageИзвор:
European Journal of Pharmaceutical Sciences, 2016, 81, 172-180Издавач:
- Elsevier
Финансирање / пројекти:
- Примена EIIP/ISM биоинформатичке платформе у откривању нових терапеутских таргета и потенцијалних терапеутских молекула (RS-MESTD-Basic Research (BR or ON)-173001)
- Фармакодинамска и фармакогеномска испитивања новијих лекова у лечењу солидних тумора (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41026)
DOI: 10.1016/j.ejps.2015.10.017
ISSN: 0928-0987; 1879-0720
PubMed: 26598394
WoS: 000367787700021
Scopus: 2-s2.0-84946239745
Колекције
Институција/група
VinčaTY - JOUR AU - Srdić-Rajić, Tatjana AU - Nikolić, Katarina M. AU - Čavić, Milena R. AU - Đokić, Ivana AU - Gemović, Branislava S. AU - Perović, Vladimir R. AU - Veljković, Nevena V. PY - 2016 UR - https://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. PB - Elsevier 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 Nikolić, Katarina M. and Čavić, Milena R. and Đokić, Ivana and Gemović, Branislava S. and Perović, Vladimir R. and Veljković, Nevena V.", year = "2016", 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.", publisher = "Elsevier", 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., Nikolić, K. M., Čavić, M. R., 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. in European Journal of Pharmaceutical Sciences Elsevier., 81, 172-180. https://doi.org/10.1016/j.ejps.2015.10.017
Srdić-Rajić T, Nikolić KM, Čavić MR, Đokić I, Gemović BS, Perović VR, Veljković NV. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. in European Journal of Pharmaceutical Sciences. 2016;81:172-180. doi:10.1016/j.ejps.2015.10.017 .
Srdić-Rajić, Tatjana, Nikolić, Katarina M., Čavić, Milena R., 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" in European Journal of Pharmaceutical Sciences, 81 (2016):172-180, https://doi.org/10.1016/j.ejps.2015.10.017 . .