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Knockdown of iPLA2γ enhances cisplatin-induced apoptosis by increasing ROS-dependent peroxidation of mitochondrial phospholipids in bladder cancer cells.
Nakayama, Satoko; Yoda, Emiko; Yamashita, Saki; Takamatsu, Yuka; Suzuki, Yasutomo; Kondo, Yukihiro; Hara, Shuntaro.
Afiliación
  • Nakayama S; Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
  • Yoda E; Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
  • Yamashita S; Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
  • Takamatsu Y; Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
  • Suzuki Y; Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
  • Kondo Y; Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
  • Hara S; Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. Electronic address: haras@pharm.showa-u.ac.jp.
Free Radic Biol Med ; 220: 301-311, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38734266
ABSTRACT
Cisplatin (CDDP) is a platinum-based drug with anti-cancer activity and is widely used as a standard therapy for bladder cancer. It is well known that CDDP causes cell death by increasing the generation of reactive oxygen species (ROS) and lipid peroxidation, but the mechanism of its anti-cancer effects has not been fully elucidated. There are still some problems such as chemoresistance in CDDP therapy. In the present study, we found the expression of Ca2+-independent phospholipase A2γ (iPLA2γ), which has been reported to regulate cellular redox homeostasis by inhibiting lipid peroxide accumulation, in human bladder cancer tissues. Thus, we investigated the effect of iPLA2γ knockdown on CDDP-induced bladder cancer cell death. As a result, we found that iPLA2γ knockdown significantly enhanced CDDP-induced apoptosis, intracellular and mitochondrial ROS production, cytochrome c release and caspase activation in bladder cancer cells. Moreover, mitochondrial membrane potential was decreased and peroxidation of mitochondrial phospholipids was increased by iPLA2γ knockdown. It was also shown that co-treatment of bromoenol lactone, an iPLA2 inhibitor, increased CDDP-induced apoptosis. These results indicated that iPLA2γ plays an important role in protecting bladder cancer cells from CDDP-induced apoptosis, and that iPLA2γ inhibitors might represent a novel strategy in CDDP-based multi-drug therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfolípidos / Neoplasias de la Vejiga Urinaria / Peroxidación de Lípido / Cisplatino / Especies Reactivas de Oxígeno / Apoptosis / Fosfolipasas A2 Grupo VI / Mitocondrias Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfolípidos / Neoplasias de la Vejiga Urinaria / Peroxidación de Lípido / Cisplatino / Especies Reactivas de Oxígeno / Apoptosis / Fosfolipasas A2 Grupo VI / Mitocondrias Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos