1. Academic Validation
  2. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells

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

  • Eur J Pharm Sci. 2016 Jan 1;81:172-80. doi: 10.1016/j.ejps.2015.10.017.
Tatjana Srdic-Rajic 1 Katarina Nikolic 2 Milena Cavic 1 Ivana Djokic 3 Branislava Gemovic 3 Vladimir Perovic 3 Nevena Veljkovic 4
Affiliations

Affiliations

  • 1 Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.
  • 2 Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000, Belgrade, Serbia.
  • 3 Center for Multidisciplinary Research, Institute of Nuclear Sciences Vinca, University of Belgrade, Mihaila Petrovica Alasa 14, 11001, Belgrade, Serbia.
  • 4 Center for Multidisciplinary Research, Institute of Nuclear Sciences Vinca, University of Belgrade, Mihaila Petrovica Alasa 14, 11001, Belgrade, Serbia. Electronic address: nevenav@vinca.rs.
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.

Keywords

Apoptosis; DNA damage; Imidazoline I1 receptor signaling; K562; Proliferation; Rilmenidine.

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