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Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment
Marchesi, Irene Fais, Milena Fiorentino, Francesco Paolo Bordoni, Valentina Sanna, Luca Zoroddu, Stefano Bagella, Luigi
Marchesi, Irene
Fais, Milena
Fiorentino, Francesco Paolo
Bordoni, Valentina
Sanna, Luca
Zoroddu, Stefano
Bagella, Luigi
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2022-03-25
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http://dx.doi.org/10.3390/ijms23073581
Abstract
Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.
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Marchesi, I.; Fais, M.; Fiorentino, F.P.; Bordoni, V.; Sanna, L.; Zoroddu, S.; Bagella, L. Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment. Int. J. Mol. Sci. 2022, 23, 3581. https://doi.org/10.3390/ijms23073581
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International Journal of Molecular Sciences, Vol. 23, Iss. 7
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