Suberoylanilide hydroxamic acid is effective in preclinical studies of medulloblastoma.

Journal of Neuro-oncology
Susan E SpillerJames M Olson

Abstract

Suberoylanilide hydroxamic acid (SAHA) has been studied in adult solid and hematologic malignancies. However, little information has been reported on the effects of SAHA on central nervous system (CNS) tumors including medulloblastoma, the most common malignant brain tumor in children. We investigated SAHA in preclinical medulloblastoma models to determine its anti-cancer efficacy as well as its ability to affect intracranial lesions when administered systemically. Tissue culture studies were performed treating primary human fibroblasts, established medulloblastoma cell lines, and primary human medulloblastoma tumors with SAHA. At 10 microM concentration, SAHA had little effect on normal fibroblasts but caused >90% apoptosis in cultured medulloblastoma cells. Primary medulloblastomas from patients were sensitive to SAHA compared to vehicle alone in ex vivo studies. In athymic mice with medulloblastoma xenograft tumors, oral SAHA resulted in apoptosis of tumor tissue and significantly slowed tumor growth. In the ND2:Smo transgenic mouse medulloblastoma model, SAHA treatment caused significant apoptosis in these cerebellar tumors. SAHA effectively induces cell death in established medulloblastoma cell lines, human patient primary...Continue Reading

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Citations

May 11, 2011·Expert Review of Anticancer Therapy·Ali Varan
Feb 9, 2012·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Jasmine LauWilliam A Weiss
Jun 10, 2009·Journal of Neuro-oncology·Rebecca DeBoerJeffrey Raizer
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May 29, 2021·Expert Review of Anticancer Therapy·Megan Rose Paul, Peter E Zage

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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