PMID: 11927016Apr 3, 2002Paper

The roles of JNK1 and Stat3 in the response of head and neck cancer cell lines to combined treatment with all-trans-retinoic acid and 5-fluorouracil

Japanese Journal of Cancer Research : Gann
Muneyuki MasudaI Bernard Weinstein

Abstract

We have used a combination of vitamin A (all-trans-retinyl palmitate), 5-fluorouracil (5-FU) and radiation to treat human head and neck squamous cell carcinoma (HNSCC). This chemoradiotherapy is called "FAR therapy." In this study we examined the effects of all-trans-retinoic acid (ATRA), the active metabolite of vitamin A, and ATRA plus 5-FU on two HNSCC cell lines (YCU-N861 and YCU-H891) to gain insight into the molecular mechanisms of FAR therapy. ATRA at 1 mM (the order of concentration found in HNSCC tumors treated with FAR therapy) inhibited cell proliferation and caused G1 cell cycle arrest in both cell lines. This was associated with a decrease in cyclin D1, an increase in p27(Kip1) and a reduction in the hyperphosphorylated form of retinoblastoma protein (pRB). With YCU-N861 cells, ATRA also caused a decrease in Bcl-2 and Bcl-X(L) and an increase in Bax. Both ATRA and 5-FU activated c-Jun N-terminal kinase (JNK) 1 and the combination of both agents resulted in additive or synergistic activation of JNK1, and also enhanced the induction of apoptosis. The YCU-H891 cells, in which the epidermal growth factor receptor (EGFR)-signal transducer and activator of transcription 3 (Stat3) pathway is constitutively activated, were...Continue Reading

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Citations

Feb 27, 2013·Drugs·Kelly Dorsey, Mark Agulnik
Jun 8, 2012·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Shih-Han HungHow Tseng
Jul 30, 2016·Oncoimmunology·Tiffany R HodgesAmy B Heimberger
Sep 1, 2007·BMC Systems Biology·André FujitaCarlos E Ferreira
Jan 8, 2008·Cell Metabolism·Antonio L SerranoPura Muñoz-Cánoves
Oct 1, 2016·Oral Oncology·Nicoleta Sinevici, Jeff O'sullivan
Jun 24, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ioannis Gkouveris, Nikolaos G Nikitakis
Jan 11, 2005·The Journal of Pathology·D B Longley, P G Johnston
Oct 25, 2008·Chemical Society Reviews·Min-Hsiung Pan, Chi-Tang Ho
May 25, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Zeguang WuQin Ning
Oct 21, 2016·MedChemComm·Bibiana I FerreiraJames B Lorens

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