title: Involvement of mitochondrial permeability transition pore opening in 7-xylosyl-10-deacetylpaclitaxel-induced apoptosis.
abstract: 7-Xylosyl-10-deacetylpaclitaxel is a natural hydrophilic paclitaxel derivative. It has long been used in Chinese clinics to treat cancer. In order to further explore the underlying intracellular target of 7-xylosyl-10-deacetylpaclitaxel towards the PC-3 cell line, the ultra-structural morphology of mitochondria, the intracellular Ca (2+), the intracellular ATP, the intracellular hydrogen peroxide and pro-apoptotic Bax and Bcl-2 protein expression were measured. Additionally, the changes of mitochondrial morphology and membrane potential ( ΔΨm) were analyzed by atomic force microscopy (AFM) and flow cytometry, respectively. Our results suggest that the intracellular target of 7-xylosyl-10-deacetylpaclitaxel may be the mitochondrial permeability transition pore (mPTP). To further evaluate this hypothesis, we assessed the effect of a specific mPTP inhibitor (cyclosporine A) on the toxic action of 7-xylosyl-10-deacetylpaclitaxel. The 7-xylosyl-10-deacetylpaclitaxel-induced decrease in mitochondrial inner transmembrane potential (ΔΨm) was abolished by the addition of cyclosporine A (CsA) in PC-3 cells, indicating that 7-xylosyl-10-deacetylpaclitaxel may target mPTP. Furthermore, treatment with 7-xylosyl-10-deacetylpaclitaxel increased ROS levels in PC-3 cells. This effect was counteracted by 10 µM cyclosporine A. These data indicate that oxidative damage is involved in mPTP.
authors.affiliation: Key Laboratory of Foresty Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, People's Republic of China.
authors.forename: Shougang
authors.initials: S
authors.lastname: Jiang
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuejie
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: C531111:7-xylosyl-10-deacetylpaclitaxel; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D017239:Paclitaxel; D002118:Calcium