Garcinol and Anacardic Acid, Natural Inhibitors of Histone Acetyltransferases, Inhibit Rhabdomyosarcoma Growth and Proliferation

Rhabdomyosarcoma (RMS) is a malignant tumour of the soft tissues. There are two main histopathological types: alveolar and embryonal. RMS occurs mainly in childhood and is a result of the deregulation of growth and differentiation of muscle cell precursors. There is an increasing amount of data indi...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-07, Vol.28 (14), p.5292
Main Authors: Tomasiak, Patrycja, Janisiak, Joanna, Rogińska, Dorota, Perużyńska, Magdalena, Machaliński, Bogusław, Tarnowski, Maciej
Format: Article
Language:English
Subjects:
Acids
Apoptosis
Cancer
Cell cycle
Cell Line, Tumor
Cell Proliferation
Chemotherapy
DNA damage
Enzymes
Epigenetic inheritance
Epigenetics
Gene expression
Growth
Histone Acetyltransferases
Histones
Histones - metabolism
Humans
inhibitors
Kinases
Rhabdomyosarcoma
Rhabdomyosarcoma - drug therapy
RMS
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Summary:Rhabdomyosarcoma (RMS) is a malignant tumour of the soft tissues. There are two main histopathological types: alveolar and embryonal. RMS occurs mainly in childhood and is a result of the deregulation of growth and differentiation of muscle cell precursors. There is an increasing amount of data indicating that numerous epigenetic alterations within chromatin and histone proteins are involved in the pathogenesis of this malignancy. Histone acetylation is one of the most important epigenetic modifications that is catalysed by enzymes from the group of histone acetyltransferases (HAT). In this study, the impact of the natural histone acetyltransferase inhibitors (HATi)-garcinol (GAR) and anacardic acid (AA)-on the biology of RMS cells was evaluated through a series of in vitro tests measuring proliferation, viability, clonogenicity, cell cycle and apoptosis. Moreover, using oligonucleotide microarrays and real-time PCR, we identified several genes whose expression changed after GAR and AA treatment. The examined HATi significantly reduce the invasive phenotype of RMS cells by inhibiting the growth rate, viability and clonogenic abilities. What is more, these substances cause cell cycle arrest in the G2/M phase, induce apoptosis and affect the genetic expression of the endoplasmic reticulum stress sensors. GAR and AA may serve as promising potential anti-cancer drugs since they sensitize the RMS cells to chemotherapeutic treatment.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28145292