Potential anti-melanoma activity of Imidazoline I1 receptor agonists
Аутори
Vidosavljević, MarijaSrdić-Rajić, Tatjana
Mitrović-Ajtić, Olivera
Jevrić, Marko
Grahovac, Jelena
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted
BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still
have poor prognosis with a median survival of 9 months and a long-term survival rate
of 10%. There is an urgent need for novel treatment modalities that target metastatic
melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that
has been shown to be a tumor suppressor in breast cancer through regulation of
cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has
not been investigated to date. Of importance, several IR1 agonists are clinically
approved for treatment of hypertension. The aim of this study was to examine the
IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell
viability. To confirm the target expression, we first determined IR1 levels in primary
and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. ...
We found that it is expressed in primary tumors and liver metastases and, to a lesser
extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists
– rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell
lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently
inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts
and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced
cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that
imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already
clinically approved agents have promising anti-cancer activity.
Извор:
5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy, 2020, 92-92Издавач:
- European Association for Cancer Research
Институција/група
Institut za medicinska istraživanjaTY - CONF AU - Vidosavljević, Marija AU - Srdić-Rajić, Tatjana AU - Mitrović-Ajtić, Olivera AU - Jevrić, Marko AU - Grahovac, Jelena PY - 2020 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1399 AB - Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still have poor prognosis with a median survival of 9 months and a long-term survival rate of 10%. There is an urgent need for novel treatment modalities that target metastatic melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that has been shown to be a tumor suppressor in breast cancer through regulation of cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has not been investigated to date. Of importance, several IR1 agonists are clinically approved for treatment of hypertension. The aim of this study was to examine the IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell viability. To confirm the target expression, we first determined IR1 levels in primary and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. We found that it is expressed in primary tumors and liver metastases and, to a lesser extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists – rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already clinically approved agents have promising anti-cancer activity. PB - European Association for Cancer Research C3 - 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy T1 - Potential anti-melanoma activity of Imidazoline I1 receptor agonists EP - 92 SP - 92 UR - https://hdl.handle.net/21.15107/rcub_rimi_1399 ER -
@conference{ author = "Vidosavljević, Marija and Srdić-Rajić, Tatjana and Mitrović-Ajtić, Olivera and Jevrić, Marko and Grahovac, Jelena", year = "2020", abstract = "Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still have poor prognosis with a median survival of 9 months and a long-term survival rate of 10%. There is an urgent need for novel treatment modalities that target metastatic melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that has been shown to be a tumor suppressor in breast cancer through regulation of cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has not been investigated to date. Of importance, several IR1 agonists are clinically approved for treatment of hypertension. The aim of this study was to examine the IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell viability. To confirm the target expression, we first determined IR1 levels in primary and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. We found that it is expressed in primary tumors and liver metastases and, to a lesser extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists – rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already clinically approved agents have promising anti-cancer activity.", publisher = "European Association for Cancer Research", journal = "5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy", title = "Potential anti-melanoma activity of Imidazoline I1 receptor agonists", pages = "92-92", url = "https://hdl.handle.net/21.15107/rcub_rimi_1399" }
Vidosavljević, M., Srdić-Rajić, T., Mitrović-Ajtić, O., Jevrić, M.,& Grahovac, J.. (2020). Potential anti-melanoma activity of Imidazoline I1 receptor agonists. in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy European Association for Cancer Research., 92-92. https://hdl.handle.net/21.15107/rcub_rimi_1399
Vidosavljević M, Srdić-Rajić T, Mitrović-Ajtić O, Jevrić M, Grahovac J. Potential anti-melanoma activity of Imidazoline I1 receptor agonists. in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy. 2020;:92-92. https://hdl.handle.net/21.15107/rcub_rimi_1399 .
Vidosavljević, Marija, Srdić-Rajić, Tatjana, Mitrović-Ajtić, Olivera, Jevrić, Marko, Grahovac, Jelena, "Potential anti-melanoma activity of Imidazoline I1 receptor agonists" in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy (2020):92-92, https://hdl.handle.net/21.15107/rcub_rimi_1399 .