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Identification and functional analysis of choline transporter in tongue cancer: A novel molecular target for tongue cancer therapy.
Nishiyama, Ryohta; Nagashima, Fumiaki; Iwao, Beniko; Kawai, Yuiko; Inoue, Kana; Midori, Arisa; Yamanaka, Tsuyoshi; Uchino, Hiroyuki; Inazu, Masato.
Afiliación
  • Nishiyama R; Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
  • Nagashima F; Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
  • Iwao B; Department of Psychiatry, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
  • Kawai Y; Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
  • Inoue K; School of Nursing, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
  • Midori A; School of Nursing, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
  • Yamanaka T; Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
  • Uchino H; Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
  • Inazu M; Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; Department of Molecular Preventive Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. Electronic address: inazu@tokyo-med.ac.jp.
J Pharmacol Sci ; 131(2): 101-9, 2016 Jun.
Article en En | MEDLINE | ID: mdl-27262903
We examined the functional characteristics of choline uptake in human tongue carcinoma using the cell line HSC-3. Furthermore, we explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. Both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were expressed, and were located in plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is pH-dependent. Several cationic drugs inhibited cell viability and [(3)H]choline uptake. Choline uptake inhibitors and choline deficiency inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1 that relies on a directed H(+) gradient as a driving force. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be the major site for the control of choline oxidation in mitochondria and hence for the supply of endogenous betaine and S-adenosyl methionine, which serves as a major methyl donor. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for tongue cancer therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Neoplasias de la Lengua / Glicoproteínas de Membrana / Antígenos CD Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Neoplasias de la Lengua / Glicoproteínas de Membrana / Antígenos CD Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón