Involvement of ALOX in resistance or sensitivity of cancer treatment via plasma membrane oxidation state.

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  • Tomita Kazuo
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ. Department of Pharmacology, Hyogo College of Medicine
  • Kuwahara Yoshikazu
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ. Radiation Biol. & Med., Faculty of Med., Tohoku Med & Pharma Univ.
  • Igarashi Kento
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ.
  • Takashi Yuko
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ. Dept. Operative Dentistry & Endodontol., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ.
  • Nagasawa Taisuke
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ.
  • Nabika Hideki
    Dept. Material and Biological Chemistry, Faculty of Sci., Yamagata Univ.
  • Tanaka Koh-ichi
    Div. Pharmacol., Dept. Pharm., Sch. Pharm., Hyogo Univ. Health Sci. Department of Pharmacology, Hyogo College of Medicine
  • Kitaknaka Junichi
    Department of Pharmacology, Hyogo College of Medicine
  • Kitanaka Nobue
    Department of Pharmacology, Hyogo College of Medicine
  • Takemura Motohiko
    Department of Pharmacology, Hyogo College of Medicine
  • Nishiyama Nobuyoshi
    Div. Pharmacol., Dept. Pharm., Sch. Pharm., Hyogo Univ. Health Sci.
  • Fukumoto Manabu
    Dept. Molecular Pathology, Tokyo Medical University
  • Nishitani Yoshihiro
    Dept. Operative Dentistry & Endodontol., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ.
  • Kurimasa Akihiro
    Radiation Biol. & Med., Faculty of Med., Tohoku Med & Pharma Univ.
  • Sato Tomoaki
    Dept. Applied Pharm., Grad. Sch. Med. & Dent. Sci. Kagoshima Univ.

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Other Title
  • がんの治療抵抗性・感受性を制御する細胞膜酸化状態とALOXの関与

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<p>Although radiation therapy is one of the choices to treat cancers and is an excellent local treatment method, existence of radiation resistant cell is a major problem. We established clinically relevant radioresistant (CRR) cells that can survive exposing to 2 Gy/day X-rays for more than 30 days. However, the mechanism to obtain resistance has not been elucidated yet. We investigated the relationships between resistant mechanism to hydrogen peroxide (H2O2) and plasma membrane state in CRR cells. </p><p>　CRR cells showed resistance to H2O2, but catalase enzyme activity was down-regulated. Plasma membrane potential were low, no internal H2O2 increase and no lipid peroxidation were seen even after 2 hours of H2O2 treatment in CRR cells. Administration of oxidized lipid led to further cell death after H2O2 treatment in CRR cells. The lipoxygenase (ALOX) gene and protein expressions were down-regulated in CRR cells. We also established stress-sensitive ρ0 cells that lack mitochondrial DNA. Gene and protein expressions of ALOX were up-regulated in ρ0 cells. Expression of cyclooxygenase-2 does not seem to be involved in this mechanism. </p><p>　These results suggest that the involvement of ALOX in resistance or sensitivity of cancer treatment.</p>

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