Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma

Oncogenesis
Marta Di MartileDonatella Del Bufalo

Abstract

Sarcomas are rare tumors with generally poor prognosis, for which current therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are emerging anti-tumor agents; however, little is known about their effect in sarcomas. By using established and patient-derived sarcoma cells with different subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro survival in a p53-independent manner. ITF2357-mediated cell death implied the activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic BH3-only proteins and a caspases-dependent mechanism. ITF2357 also induced autophagy, which protected sarcoma cells from apoptotic cell death. ITF2357 activated forkhead box (FOXO) 1 and 3a transcription factors and their downstream target genes, however, silencing of both FOXO1 and 3a did not protect sarcoma cells against ITF2357-induced apoptosis and upregulated FOXO4 and 6. Notably, ITF2357 synergized with Doxorubicin to induce cell death of established and patient-derived sarcoma cells. Furthermore, combination treatment strongly impaired xenograft tumor growth in vivo, when compared to single treatments, suggesting that combination of ITF2357 with Doxorubicin has the potential to enhanc...Continue Reading

References

May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gonzalo LopezDina C Lev
Oct 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew A Lane, Bruce A Chabner
Feb 6, 2010·Journal of Hematology & Oncology·Jiahuai TanDelong Liu
Feb 1, 2011·Biochimica Et Biophysica Acta·Lucia Di MarcotullioAlberto Gulino
Mar 9, 2013·Cell Death & Disease·Y RagazzoniD Trisciuoglio
Aug 3, 2013·The Journal of the American Academy of Orthopaedic Surgeons·Brian E Walczak, Ronald B Irwin
Mar 22, 2014·International Journal of Cancer. Journal International Du Cancer·Roberta ZappasodiMassimo Di Nicola
Oct 9, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A Le CesneW T A Van Der Graaf
Oct 24, 2014·Cell Death & Disease·L MaB Brodin
Dec 2, 2014·Pediatric Clinics of North America·Josephine H HaDuongLeo Mascarenhas
Jan 30, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Q S-C ChuE A Eisenhauer
Feb 11, 2015·World Journal of Pharmacology·Shubhalaxmi KayarthodiE Shyam P Reddy
Jul 17, 2015·Radiation Oncology·Claudia BlattmannJürgen Debus
Sep 24, 2015·Molecular Cancer Research : MCR·Gonzalo LopezRaphael E Pollock
Dec 22, 2015·Cellular and Molecular Life Sciences : CMLS·Alexandra Coomans de Brachène, Jean-Baptiste Demoulin
Feb 24, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S ThomasP N Munster
Apr 12, 2016·Frontiers in Oncology·Maria FerraiuoloSabrina Strano
Jan 23, 2017·BMC Cancer·Sridhar MurahariWilliam C Kisseberth

❮ Previous
Next ❯

Citations

Sep 27, 2018·Cell Death & Disease·Sara IachettiniAnnamaria Biroccio
Apr 23, 2020·Sarcoma·Kirill I KirsanovMarianna G Yakubovskaya
Jul 14, 2018·BioMed Research International·Jana S MilesHernan Flores-Rozas
Oct 8, 2020·Frontiers in Genetics·Lourdes Hontecillas-PrietoDaniel J García-Domínguez
Feb 13, 2021·Genes·Aleksandra Majchrzak-CelińskaMikołaj Szoszkiewicz
Apr 20, 2021·Life Sciences·M Janaki RamaiahRajasekhar Reddy Manyam

❮ Previous
Next ❯

Methods Mentioned

BETA
histone acetylation
xenografts
acetylation
PCR
fluorescence microscopy
xenograft
light microscopy

Software Mentioned

Calcusyn

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms