Pheophorbide a based photodynamic therapy induces apoptosis via mitochondrial-mediated pathway in human uterine carcinosarcoma
Pheophorbide a based photodynamic therapy induces apoptosis via mitochondrial-mediated pathway in human uterine carcinosarcoma
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DOI：
10.4161/cbt.8.6.7694
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发表时间：
2009-03-15
影响因子：
3.6
通讯作者：
Fung, Kwok-Pui
中科院分区：
文献类型：
--
作者：
Tang, Patrick Ming-Kuen;Liu, Xiao-Zhuo;Fung, Kwok-Pui
子宫癌肉瘤是一种侵袭性肿瘤，由于缺乏非常有效的化疗方案，生存率较低。最近认为光动力疗法（PDT）是治疗这种癌症的有效方案。脱镁叶绿酸 a (Pa) 是绿色植物细胞中叶绿素的降解产物，通过 PDT 方法报道了其对多种人类癌细胞的抗肿瘤作用。本研究表明，在PDT中使用Pa（Pa-PDT）可显着抑制人子宫肉瘤细胞系MES-SA，24小时时IC50值为0.5μM。根据碘化丙啶(PI)染色、膜联蛋白-V染色和DNA片段化测定的结果，发现Pa-PDT处理的细胞诱导凋亡。 Pa被发现位于线粒体中，在光照射期间快速产生单线态氧，导致线粒体膜电位去极化，其中检测到细胞色素c的释放，并导致MES-SA细胞中内在凋亡途径的激活。我们的研究结果揭示了 Pa-PDT 对人类子宫癌的治疗潜力。
Uterine carcinosarcoma is an aggressive neoplasm with low survival rates because of the lack of very effective chemotherapy protocol. Photodynamic therapy (PDT) is recently suggested to be an efficient protocol for this cancer. Pheophorbide a (Pa) is a chlorophyll degradation product in the green plant cells, its antitumor effect was reported on a number of human cancer cells with PDT approach. This study demonstrated that using Pa in PDT (Pa-PDT) significantly inhibited the human uterine sarcoma cell line MES-SA with an IC50 value of 0.5 mu M at 24 h. Induction of apoptosis was found on the Pa-PDT treated cells according to the results of propidium iodide (PI) staining, annexin-V staining and DNA fragmentation assay. Pa was found to be localized in the mitochondria that lead to the depolarization of mitochondrial membrane potential by the rapid generation of singlet oxygen during light irradiation, where release of cytochrome c was detected and lead to the activation of intrinsic apoptotic pathway in MES-SA cells. Our findings revealed the therapeutic potential of Pa-PDT on the human uterine cancer.