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Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes
Platais, C. Radhakrishnan, R. Ebensberger, S.N. Morgan, Richard Lambert, D.W. Hunter, K.D.
Platais, C.
Radhakrishnan, R.
Ebensberger, S.N.
Morgan, Richard
Lambert, D.W.
Hunter, K.D.
Publication Date
2018-07
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© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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openAccess
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20/06/2018
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Abstract
Background: High HOX gene expression has been described in many cancers, including oral squamous cell
carcinoma and the functional roles of these genes are gradually being understood. The pattern of overexpression
suggests that inhibition may be useful therapeutically. Inhibition of HOX protein binding to PBX cofactors by the
use of synthetic peptides, such as HXR9, results in apoptosis in multiple cancers.
Methods: Activity of the HOX-PBX inhibiting peptide HXR9 was tested in immortalised normal oral (NOK),
potentially-malignant (PMOL) and squamous cell carcinoma (OSCC) cells, compared to the inactive peptide
CXR9. Cytotoxicity was assessed by LDH assay. Expression of PBX1/2 and c-Fos was assessed by qPCR and
western blotting. Apoptosis was assessed by Annexin-V assay.
Results: PMOL and OSCC cells expressed PBX1/2. HOX-PBX inhibition by HXR9 caused death of PMOL and
OSCC cells, but not NOKs. HXR9 treatment resulted in apoptosis and increased expression of c-Fos in some
cells, whereas CXR9 did not. A correlation was observed between HOX expression and resistance to HXR9.
Conclusion: Inhibition of HOX-PBX interactions causes selective apoptosis of OSCC/PMOL, indicating selective
toxicity that may be useful clinically.
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Citation
Platais C, Radhakrishnan R, Ebensberger SN et al (2018) Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes. BMC Cancer. 18:723.
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Article