title: Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of canine breast cancer cells.
abstract: Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related photosensitize for photodynamic therapy (PDT). There still remains unknown changes regarding the mitochondrial in canine breast cancer cells treated with HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on structure and dysfunction of mitochondrial in cancer cells. The experimental approach included an initial study on the uptake of HMME using microscopic observation of the HMME-treated cells, optimization of the PDT-induced cell death by the MTT assay. These cells were then treated with HMME and a He-Ne laser at the wavelength of 632.8 nm following our optimized condition. Examination of mitochondrial changes by observing the stained cells under light microscope, mitochjondrial membrane potential flow cytometry, measuring the Ca(2+), SOD/GSH activity, ATPase and MDA contents for the mitochondria functions. The kinetics of HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8 J/cm(2) laser irradiation was had the maximal impact on cell viability. This treatment resulted in structural changes in mitochondria that were accompanied with the loss of mitochjondrial membrane potential. As a result, HMME-PDT increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of calcium, and decreased mitochondrial ATPase activity. The combination of these abnormalities led to accumulation of ROS in mitochondrial to high levels, which in turn contributed to HMME-PDT-induced damages of mitochondrial structure and mitochondrial dysfunction.
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China; Department of Veterinary Clinic, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
authors.forename: H T
authors.initials: HT
authors.lastname: Li
authors.forename: X Y
authors.initials: XY
authors.lastname: Song
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
authors.forename: W R
authors.initials: WR
authors.lastname: Tian
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004285:Dogs; D005260:Female; D006415:Hematoporphyrins / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D006415:Hematoporphyrins; D017319:Photosensitizing Agents
keywords: CHMm cells; Hematoporphyrin monomethyl ether; Mitochondrial dysfunction; Mitochondrial structure; PDT