Ectopic expression of Protein kinase C-beta sensitizes head and neck squamous cell carcinoma to diterpene esters

Adams, Ryan A., D'Souza, Marjorie M. A., Pierce, Carly J., Korica, Natasa, Wallwork, Ben, Parsons, Peter G., Panizza, Benedict and Boyle, Glen M. (2015) Ectopic expression of Protein kinase C-beta sensitizes head and neck squamous cell carcinoma to diterpene esters. Anticancer Research, 35 3: 1291-1296.

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Name Description MIMEType Size Downloads
Author Adams, Ryan A.
D'Souza, Marjorie M. A.
Pierce, Carly J.
Korica, Natasa
Wallwork, Ben
Parsons, Peter G.
Panizza, Benedict
Boyle, Glen M.
Title Ectopic expression of Protein kinase C-beta sensitizes head and neck squamous cell carcinoma to diterpene esters
Formatted title
Ectopic expression of Protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters
Journal name Anticancer Research   Check publisher's open access policy
ISSN 0250-7005
1791-7530
Publication date 2015-03
Sub-type Article (original research)
Open Access Status Not Open Access
Volume 35
Issue 3
Start page 1291
End page 1296
Total pages 6
Place of publication Kapandriti Attica, Attiki, Greece
Publisher International Institute of Anticancer Research
Collection year 2016
Language eng
Formatted abstract
Background: The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC.

Materials and Methods: The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified.

Results: Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005.

Conclusion: Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy.
Keyword Protein kinase C
HNSCC
TPA
PEP005
Diterpene
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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Created: Wed, 11 Mar 2015, 21:47:12 EST by Dr Benedict Panizza on behalf of Surgery - Princess Alexandra Hospital