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Antiproliferative effect of the histone demethylase inhibitor GSK‐J4 in chondrosarcomas
Author(s) -
Lhuissier Eva,
AuryLandas Juliette,
Allas Lyess,
Boittin Martine,
Boumediene Karim,
Baugé Catherine
Publication year - 2019
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2110
Subject(s) - cisplatin , propidium iodide , apoptosis , demethylase , cell growth , chemistry , cancer research , flow cytometry , cell cycle , histone , programmed cell death , microbiology and biotechnology , biology , chemotherapy , medicine , dna , biochemistry
Chondrosarcoma (CS) is the second most common malignant bone sarcoma. Its treatment remains an issue, because this tumor is radio‐ and chemo‐resistant. In the present study, we investigated the antitumoral potential of GSK‐J4, a small molecule described as an inhibitor of histone demethylases UTX and JMJD3 (KDM6A and KDM6B), alone or in combination with cisplatin in CSs. Human CS‐derived cell lines were treated with GSK‐J4 in the presence or not of cisplatin. Survival curves were established and cell proliferation and cycle were evaluated by flow cytometry using dividing cell tracking technique utilizing carboxyfluorescein succinimidyl ester labeling, or DNA staining by propidium iodide. Apoptosis and senescence were also investigated. GSK‐J4 decreased proliferation of CS cells. Additionally, it induced apoptosis in CH2879 and JJ012 cells, but not in SW1353 CSs. In addition, its association with cisplatin decreased cell proliferation more than drugs alone, whereas it did not increase apoptosis compared to cisplatin alone. Interestingly, GSK‐J4 alone as well as in association with cisplatin did not affect chondrocyte survival or proliferation. In conclusion, this study suggests that demethylase inhibitors may be useful in improving therapy for CS in reducing its proliferation.