title: Involvement of the mitochondria-caspase pathway in HeLa cell death induced by 2-ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B (EAHB)-mediated photodynamic therapy.
abstract: In order to elucidate the mechanism of cytotoxicity photoinduced by 2-ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B (EAHB), a derivative of hypocrellin B (HB), cellular uptake, subcellular localization as well as photodynamic therapy (PDT) efficiency of EAHB, and cell apoptosis photoinduced by EAHB were investigated in HeLa cells by laser confocal fluorescence microscopy, 3-(4,5-Dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, flow cytometry, DNA fragmentation on agarose gel, and Western blot. The results showed EAHB was distributed throughout the cytoplasm of the cell, with no detectable penetration into the nucleus. The proportion of dead cells increased with increases in both the dosage of light and the concentration of EAHB. Its phototoxicity to HeLa cells proceeded via apoptosis. The EAHB-PDT treatment induced a cytochrome c release from the mitochondria into the cytosol followed by the activation of both caspase 3 and caspase 9 in HeLa cells. The results suggested that EAHB-PDT treatment induced apoptosis in HeLa cells, and the cellular apoptosis involved a mitochondria-/caspase-dependent mechanism.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China. zhouzhixiang@bjut.edu.cn
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Wang
authors.initials: W
authors.lastname: Sheng
authors.forename: Zelin
authors.initials: Z
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Rugang
authors.initials: R
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*
chemical_list: C578600:2-ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B; D017319:Photosensitizing Agents; D011804:Quinolines; D010569:Perylene; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9