title: Intracellular distribution and mechanisms of actions of photosensitizer Zinc(II)-phthalocyanine solubilized in Cremophor EL against human hepatocellular carcinoma HepG2 cells.
abstract: Zinc(II)-phthalocyanine (ZnPc) is a metal photosensitizer. In the present study, we formulated the poorly-soluble ZnPc in Cremophor EL solution to enhance its solubility and determined its intracellular distribution and mechanisms of action on human hepatocellular carcinoma HepG2 cells. ZnPc uptake by the cells reached a plateau by 8h. ZnPc primarily located in mitochondria, lysosome and endoplasmic reticulum. The concentration-growth inhibition curves of ZnPc on the cell lines were pharmacodynamically enhanced by 10-50 folds by irradiation. Once irradiated, ZnPc produced significant amount of reactive oxygen species (ROS), activated caspase-3 and caspase-9, arrested cell cycle mainly at G2/M stage, and decreased membrane potential (ΔΨm) of HepG2 cells. In conclusion, the present study first elucidated cellular and molecular mechanisms of ZnPc on HepG2 cells.
authors.affiliation: College of Chemistry and Chemical Engineering, Fuzhou University, 523 Industry Road, Science Building, 3FL., Fuzhou, Fujian 350002, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Dai
authors.forename: Wenna
authors.initials: W
authors.lastname: Zhao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xie
authors.forename: Jinping
authors.initials: J
authors.lastname: Xue
authors.forename: Jianhui
authors.initials: J
authors.lastname: Ye
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C063072:zinc(II) phthalocyanine trisulfonic acid; C000515:cremophor EL; D053148:Caspase 3; D053453:Caspase 9; D005990:Glycerol