Proteomic Analysis of Apoptosis Induced by Xanthoangelol, a Major Constituent of Angelica keiskei, in Neuroblastoma(Pharmacology)

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概要

• 論文の詳細を見る

• Neuroblastoma is the most common solid tumor in children. Despite aggressive chemotherapy, the prognosis of patients with advanced neuroblastoma is still very poor. Our recent study showed that xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, induced caspase-3-dependent apoptosis in neuroblastoma cells. However, details of the mechanism underlying its apoptotic action are still unclear. Here we show that xanthoangelol triggers oxidative stress by generation of reactive oxygen species and induces apoptosis through release of cytochrome c and activation of caspase-9 in IMR-32 cells. Pretreatment with an antioxidant, vitamin E, prevented the increase of reactive oxygen species and apoptosis induced by xanthoangelol. Proteomic analysis using 2-dimensional electrophoresis and MALDI-TOF-MS revealed that DJ-1 protein was involved in xanthoangelol-induced apoptosis. DJ-1 responded to its oxidative stress status by being oxidized itself. Furthermore, DJ-1 was down-regulated by xanthoangelol, leading to loss of antioxidant function and acceleration of apoptosis. We also show that xanthoangelol has a cytotoxic effect on drug-resistant LA-N-1 and NB-39 cells as well as drug-sensitive IMR-32 and SK-N-SH cells. These findings suggest that xanthoangelol induces apoptosis by increasing reactive oxygen species and targeting DJ-1, and such mechanism may be an effective therapeutic approach for advanced neuroblastoma.

• 社団法人日本薬学会の論文
• 2008-04-01

著者

• ABIKO Yoshimitsu

  Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo

• Tabata Keiichi

  日本大学 薬学部臨床医学ユニット

• Motani Kou

  Research Unit Of Clinical Medicine College Of Pharmacy Nihon University

• Motani Kou

  日本大学 薬学部臨床医学ユニット

• Suzuki T

  Department Of Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences:core Research Fo

• Kimura Y

  Coll. Of Pharmacy Nihon Univ.

• SUZUKI Takashi

  Research Institute for Scientific Measurements,Tohoku University

• TABATA Keiichi

  Research Unit of Clinical Medicine, College of Pharmacy, Nihon University

• KIMURA Yumiko

  Research Unit of Analytical Chemistry of Pharmaceuticals, College of Pharmacy, Nihon University

• OKANO Soichiro

  Department of Biochemistry and Molecular Biology, School of Dentistry at Matsudo, Nihon University

• SHIBATA Yasuko

  Department of Biochemistry and Molecular Biology, School of Dentistry at Matsudo, Nihon University

• NAGAI Hisashi

  Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University

• AKIHISA Toshihiro

  Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University

• Nagai Hisashi

  Department Of Electrical Engineering Kyoto University

• Okano Soichiro

  Department Of Biochemistry And Molecular Biology School Of Dentistry At Matsudo Nihon University

• Shibata Yasuko

  日本大学 薬学部臨床医学ユニット

• Suzuki T

  Department Of Pharmaceutics College Of Pharmacy Nihon University

• Suzuki Takashi

  School Of Pharmacy Nihon Univ.

• Shibata Yasuko

  Department Of Biochemistry And Molecular Biology Nihon University School Of Dentistry At Matsudo:res

• Abiko Yoshimitsu

  Department Of Biochemistry And Molecular Biology School Of Dentistry At Matsudo Nihon University

• Yasukawa Ken

  Coll. Of Pharmacy Nihon Univ.

• Akihisa T

  College Of Pharmacy Nihon University

• Akihisa Toshihiro

  日本大学 理工学部

• Akihisa Toshihiro

  Department Of Materials And Applied Chemistry Collegeof Science And Technology Nihon University

• Akihisa Toshihiro

  College Of Science And Technology Nihon University

• Suganuma Taiyo

  (pressent Address)department Of Pharmacology Tokyo Women's Medical University

• Suzuki Takashi

  Department Of Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences:core Research Fo

• Abiko Yoshimitsu

  Department Of Biochemistry And Molecular Biochemistry Nihon University School Of Dentistry At Matsud

• Okano Soichiro

  Department Of Biochemistry And Molecular Biology Nihon University School Of Dentistry At Matsudo

• Shibata Yasuyo

  Department Of Biochemistry And Molecular Biology Nihon University School Of Dentistry At Matsudo

• Tabata Keiichi

  School Of Pharmacy Nihon University

• Takase S

  College Of Science And Technology (funabashi Campus) Nihon University

• Suzuki Takashi

  Research Faculty Of Agriculture Hokkaido University

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