GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F16%3A10326654" target="_blank" >RIV/00216208:11110/16:10326654 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.3892/ijo.2016.3596" target="_blank" >http://dx.doi.org/10.3892/ijo.2016.3596</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/ijo.2016.3596" target="_blank" >10.3892/ijo.2016.3596</a>

Result language

angličtina

Original language name

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

Original language description

MEK kinase inhibitors (trametinib and selumetinib) or kinase inhibitors directed against mutated BRAF(V600E) (vemurafenib and dabrafenib) have initial encouraging effects in the treatment of melanoma but acquired resistance appears almost invariably after some months. Studies revealed mutually exclusive NRAS and BRAF activating mutations driving the MAPK/ERK pathway among human melanomas. Although combination therapy exerts significantly better antitumor cell efficacy, complete remission is rarely achieved. To employ an alternative approach, we have targeted the Hedgehog/GLI pathway, which is deregulated in melanomas, through the GLI1/2 inhibitor GANT61, alone or accompanied with the treatment by the BCL2 family inhibitor obatoclax in 9 melanoma cell lines. Thus, we targeted melanoma cells irrespective of their NRAS or BRAF mutational status. After GANT61 treatment, the cell viability was drastically diminished via apoptosis, as substantial nuclear DNA fragmentation was detected. In all tested melanoma cell lines, the combined treatment was more efficient than the application of each drug alone at the end of the cell growth with inhibitors. GANT61 was efficient also alone in most cell lines without the addition of obatoclax, which had only a limited effect when used as a single drug. In most cell lines, tumor cells were eradicated after 5-9 days of combined treatment in colony outgrowth assay. To conclude, GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

<a href="/en/project/NT14005" target="_blank" >NT14005: Hedgehog-GLI signalling: an indicator of the tumor biological behavior in melanoma, lung cancer and some other tumors and its blocking as an antitumor therapy</a><br>

Continuities

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

Publication year

2016

Confidentiality

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

Name of the periodical

International Journal of Oncology

ISSN

1019-6439

e-ISSN

—

Volume of the periodical

49

Issue of the periodical within the volume

3

Country of publishing house

GR - GREECE

Number of pages

8

Pages from-to

953-960

UT code for WoS article

000382447300010

EID of the result in the Scopus database

2-s2.0-84978476468