Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity

The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic str...

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Main Authors: Voon, Y.L., Ahmad, M., Wong, P.F., Husaini, R., Ng, W.T.W., Leong, C.O., Lane, D.P., Khoo, A.S.B.
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Published: Spandidos Publications 2015
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Online Access:http://eprints.um.edu.my/19489/
http://dx.doi.org/10.3892/or.2015.4177
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spelling my.um.eprints.194892018-10-01T02:13:04Z http://eprints.um.edu.my/19489/ Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity Voon, Y.L. Ahmad, M. Wong, P.F. Husaini, R. Ng, W.T.W. Leong, C.O. Lane, D.P. Khoo, A.S.B. R Medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic strategy for NPC. In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53. Treatment with Nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin. The combined treatment also markedly suppressed soft agar colony growth formation and increased apoptosis of NPC cells. The effect of Nutlin-3 on NPC cells was inhibited by knockdown of p53, suggesting that its effect was p53-dependent. Extended treatment with increasing concentrations of Nutlin-3 did not result in emergence of p53 mutations in the C666-1 cells. Collectively, the present study revealed supportive evidence of the effectiveness of combining cisplatin and Nutlin-3 as a potential therapy against NPC. Spandidos Publications 2015 Article PeerReviewed Voon, Y.L. and Ahmad, M. and Wong, P.F. and Husaini, R. and Ng, W.T.W. and Leong, C.O. and Lane, D.P. and Khoo, A.S.B. (2015) Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity. Oncology Reports, 34 (4). pp. 1692-1700. ISSN 1021-335X http://dx.doi.org/10.3892/or.2015.4177 doi:10.3892/or.2015.4177
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
RM Therapeutics. Pharmacology
RS Pharmacy and materia medica
spellingShingle R Medicine
RM Therapeutics. Pharmacology
RS Pharmacy and materia medica
Voon, Y.L.
Ahmad, M.
Wong, P.F.
Husaini, R.
Ng, W.T.W.
Leong, C.O.
Lane, D.P.
Khoo, A.S.B.
Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
description The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic strategy for NPC. In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53. Treatment with Nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin. The combined treatment also markedly suppressed soft agar colony growth formation and increased apoptosis of NPC cells. The effect of Nutlin-3 on NPC cells was inhibited by knockdown of p53, suggesting that its effect was p53-dependent. Extended treatment with increasing concentrations of Nutlin-3 did not result in emergence of p53 mutations in the C666-1 cells. Collectively, the present study revealed supportive evidence of the effectiveness of combining cisplatin and Nutlin-3 as a potential therapy against NPC.
format Article
author Voon, Y.L.
Ahmad, M.
Wong, P.F.
Husaini, R.
Ng, W.T.W.
Leong, C.O.
Lane, D.P.
Khoo, A.S.B.
author_facet Voon, Y.L.
Ahmad, M.
Wong, P.F.
Husaini, R.
Ng, W.T.W.
Leong, C.O.
Lane, D.P.
Khoo, A.S.B.
author_sort Voon, Y.L.
title Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
title_short Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
title_full Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
title_fullStr Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
title_full_unstemmed Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
title_sort nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
publisher Spandidos Publications
publishDate 2015
url http://eprints.um.edu.my/19489/
http://dx.doi.org/10.3892/or.2015.4177
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