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The novel atypical retinoid ST 5589 down‐regulates Aurora Kinase A and has anti‐tumour activity in lymphoma pre‐clinical models
Author(s) -
Bernasconi Elena,
Gaudio Eugenio,
Kwee Ivo,
Rinaldi Andrea,
Cascione Luciano,
Tarantelli Chiara,
Mensah Afua Adjeiwaa,
Stathis Anastasios,
Zucca Emanuele,
Vesci Loredana,
Giannini Giuseppe,
Bertoni Francesco
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13595
Subject(s) - cancer research , lymphoma , cell culture , apoptosis , kinase , biology , medicine , immunology , microbiology and biotechnology , genetics
Summary Despite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti‐cancer activity. Here, we report the preclinical activity of a new member of this class, the ST 1926‐derivative ST 5589, in lymphomas. ST 5589 presented a dose‐dependent anti‐proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM . Apoptosis was observed in 8/11 cell lines. ST 5589 induced changes in the gene expression profiles of the cell lines, including the down‐regulation of Aurora Kinase A ( AURKA ). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST 5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti‐tumour activity of ST 5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti‐cancer compounds, and the encouraging results obtained with the new ST 1926‐derivative ST 5589 provide the basis for further developments of the compound.