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Down-regulation of adenine nucleotide translocase 3 and its role in camptothecin-induced apoptosis in human hepatoma QGY7703 cells
Authors:Zhenlin Hu  Xueqing Guo  Qi Yu  Jianzhong Li  Cheng Guo  Junping Zhang
Affiliation:a Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
b State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China
c Department of Pharmacy, Sixth Affiliated People Hospital, Shanghai Jiaotong University, Shanghai 200233, China
Abstract:Adenine nucleotide translocase (ANT) is known as a core component of the mitochondrial permeability transition pore (MPTP) and a key player in cell death. However, its role in camptothecin (CPT)-induced apoptosis has not been examined. We showed that CPT-induced apoptosis in QGY7703 cells and down-regulated the expression of ANT3. Using ANT3 knock-out and overexpression experiments, we provide further evidence that ANT3 plays a contributive role in CPT-induced apoptosis through induction of MPTP. We speculate that the down-regulation of ANT3 upon stimulation with CPT may be part of the molecular basis underlying the mechanism of acquired resistance to CPT.
Keywords:ANT, adenine nucleotide translocase   CPT, camptothecin   MPTP, mitochondrial permeability transition pore   ΔΨm, mitochondrial membrane potential
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