title: In vitro evaluation of ruthenium complexes for photodynamic therapy.
abstract: BACKGROUND
  Photodynamic therapy (PDT) is a promising anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDT mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated.
  
  
  METHODS
  Photocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization. Mitochondrial membrane potential (MMP), cell apoptosis, DNA fragmentation, c-Myc gene expression, and telomerase activities were also assayed.
  
  
  RESULTS
  Rup-03 and Rup-04 had the lowest IC50values. Rup-03 had an IC50value of 29.5±2.3μM in HepG2 cells and 59.0±6.1μM in RAW264.7 cells, while Rup-04 had an IC50value of 40.0±3.8μM in SGC-7901 cells. The complexes also induced cellular morphological changes and impaired cellular ability to scavenge ROS, and accumulated preferentially in mitochondria and endoplasmic reticulum. Rup-03 reduced MMP levels, induced apoptosis, and repressed both c-Myc mRNA expression and telomerase activity in HepG2 cells.
  
  
  CONCLUSIONS
  Among six candidates, Rup-03-mediated PDT is most effective against HepG2 and RAW264.7, with a similar efficacy as that of Rup-04-mediated PDT against SGC-7901 cells. Repression of ROS scavenging activities and c-Myc expression, which mediated DNA damage-induced cell apoptosis and repression of telomerase activity, respectively, were found to be involved in the anticancer mechanisms of Rup-03.
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China. Electronic address: lielizabeth@126.com.
authors.forename: Wenna
authors.initials: W
authors.lastname: Li
authors.affiliation: The Third Affiliation Hospital, Sun Yat-Sen University, Guangzhou, 510275, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Linglin
authors.initials: L
authors.lastname: Lai
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Peng
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Ennian
authors.initials: E
authors.lastname: Leng
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Sun
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: wenjiemei@126.com.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Mei
authors.affiliation: Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000138:chemical synthesis*; D000067996:RAW 264.7 Cells; D012428:Ruthenium / Q000008:administration & dosage* / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D012428:Ruthenium
keywords: Apoptosis; Photodynamic therapy; Porphyrin; Ruthenium (II) complexes