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Inhibition of histone deacetylase 3 stimulates apoptosis induced by heat shock under acidic conditions in human maxillary cancer

Oncogene volume 24, pages 7346–7354 (2005)Cite this article

Abstract

To elucidate the molecular mechanisms for the enhancement of heat-induced apoptosis on exposure to acidic conditions, human maxillary carcinoma IMC-3 cells were heat-shocked at 44°C for 30 min at either pH 7.4 or 6.7. Analyses with cDNA arrays, the reverse transcription–polymerase chain reaction (RT–PCR), and Western blotting were performed. We found that histone deacetylase 3 (HDAC3) was specifically induced after hyperthermia at 44°C for 30 min at pH 6.7. Although the cytotoxicity of heating at 44°C for 30 min was enhanced by decreasing the pH from 7.4 to 6.7, it was enhanced even more by antisense RNA oligonucleotides for HDAC3. The induction of G2/M arrest after heating occurred earlier at pH 6.7 than at pH 7.4. The inhibition of HDAC3 by the antisense RNA oligonucleotides suppressed partially the induction of G2/M arrest, resulting in an enhancement of the apoptosis caused by the heating under acidic conditions. Antisense RNA oligonucleotides for HDAC3 enhanced apoptosis 48 h after hyperthermia at 43°C for 30 min in vivo. Analyses of p65 activity suggested that NF-κB is involved in this enhancement of hyperthermia. HDAC3 may be a novel target enhancing hyperthermia and combined treatment with hyperthermia and HDAC inhibitors is a possible modality for cancer therapy.

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Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research and Scientific Research on Priority Area (C) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Drs C Sugimoto, H Sunaga, H Igawa, Y Kimura and H Yamamoto (Department of Otorhinolaryngology, Fukui Medical University) for a critical review of this study. We are also grateful to Ms Kazumi Uno for excellent technical assistance.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, University of Fukui, Matsuoka, 910-1193, Fukui, Japan

    Norihiko Narita, Shigeharu Fujieda, Masaharu Tokuriki, Noboru Takahashi, Hideaki Tsuzuki & Toshio Ohtsubo

  2. Department of Experimental Radiology and Health Physics, Faculty of Medical Science, University of Fukui, Matsuoka, 910-1193, Fukui, Japan

    Hideki Matsumoto

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  1. Norihiko Narita
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Correspondence to Norihiko Narita.

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Narita, N., Fujieda, S., Tokuriki, M. et al. Inhibition of histone deacetylase 3 stimulates apoptosis induced by heat shock under acidic conditions in human maxillary cancer. Oncogene 24, 7346–7354 (2005). https://doi.org/10.1038/sj.onc.1208879

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