| Cytotoxic activity of the histone deacetylase inhibitor panobinostat (LBH589) in anaplastic thyroid cancer in vitro and in vivo. | |
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MedLine Citation:
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PMID: 21400508 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Anaplastic thyroid carcinoma has a rapidly fatal clinical course, being resistant to multimodal treatments. Microtubules, α/β tubulin heterodimers, are crucial in cell signaling, division and mitosis and are among the most successful targets for anticancer therapy. Panobinostat (LBH589) is a potent deacetylase inhibitor acting both on histones and non-histonic proteins, including α-tubulin. In vitro LBH589, evaluated in three anaplastic thyroid carcinoma cell lines (BHT-101, CAL-62, 8305C), resulted in impairment of cell viability, inhibition of colony formation, cell cycle arrest, and apoptosis induction. Mechanistically, we showed that LBH589 not only affected the expression of p21 and cyclin D1, but markedly determined microtubule stabilization as evidenced by tubulin acetylation and increased tubulin polymerization. In a SCID xenograft model implanted with CAL-62 cells, the cytotoxic properties of LBH589 were confirmed. The drug at the dose of 20 mg/kg significantly impaired tumour growth (final tumour volume 2.5 fold smaller than in untreated animals); at this dose no relevant side effects were observed. In tumours of treated animals, a significant reduction of Ki67, which was negatively correlated with tubulin acetylation, was observed. Moreover, acetyl-tubulin levels negatively correlated with tumour volume at sacrifice, reinforcing the opinion that tubulin acetylation has a role in the inhibition of tumour growth. In conclusion, LBH589, acting on both histones and non histonic proteins in anaplastic thyroid cancer, appears to be a promising therapeutic agent for the treatment of this kind of cancer which is known not to respond to conventional therapy. |
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Authors:
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Maria Graziella Catalano; Mariateresa Pugliese; Eleonora Gargantini; Cristina Grange; Benedetta Bussolati; Sofia Asioli; Ornella Bosco; Roberta Poli; Alessandra Compagnone; Andrea Bandino; Franco Mainini; Nicoletta Fortunati; Giuseppe Boccuzzi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-11 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: - ISSN: 1097-0215 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Dept. Clinical Pathophysiology, University of Turin, Torino, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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