title: Inhibition of cancer cell growth by ruthenium complexes.
abstract: BACKGROUND
  Previous studies suggest that certain transition metal complexes, such as cisplatin, are efficacious for treating various cancer types, including ovarian, lung, and breast.
  
  
  METHODS
  In order to further evaluate ruthenium (Ru) complexes as potential anti-cancer agents, we synthesized and evaluated Ru-arene complexes. Two complexes with the general formula [Ru (η (6)-p-cym) (N-N) Cl](+) were tested for their abilities to inhibit cancer cells.
  
  
  RESULTS
  The complex with o-phenylenediamine as the N-N ligand (o-PDA) significantly inhibited growth of breast (MDA-MB-231, MCF-7, SKBR-3, and SUM149), lymphoma (Raji), melanoma (Bowes), and osteosarcoma (HT1080); however, the complex with o-benzoquinonediimine (o-BQDI) was ineffective except for SUM149. In contrast, o-PDA failed to inhibit growth of human breast epithelial cells, MCF-10A. Treatment of MDA-MBA-231 cells with o-PDA resulted in a significant reduction of productions of PDGF-AA, GM-CSF, and VEGF-A proteins at the transcriptional levels. Finally, we demonstrated that o-PDA synergistically inhibited MDA-MB-231 cell growth with cyclophosphamide but not doxorubicin or paclitaxel.
  
  
  CONCLUSIONS
  These results suggest that Ru-arene complexes are promising anti-cancer drugs that inhibit progression and metastasis by blocking multiple processes for breast and other types of cancer.
authors: Department of Cell Biology, Windber Research Institute, 620 7th Street, Windber, PA, 15963, USA. g.iida@wriwindber.org.|Murtha Cancer Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA. g.iida@wriwindber.org.
authors: Joji
authors: J
authors: Iida
authors: Department of Chemistry, University of Pittsburgh at Johnstown, 450 Schoolhouse Road, Johnstown, PA, 15904, USA. etbell@pitt.edu.
authors: Elisabeth T
authors: ET
authors: Bell-Loncella
authors: Department of Cell Biology, Windber Research Institute, 620 7th Street, Windber, PA, 15963, USA. m.purazo@wriwindber.org.
authors: Marc L
authors: ML
authors: Purazo
authors: Department of Chemistry, University of Pittsburgh at Johnstown, 450 Schoolhouse Road, Johnstown, PA, 15904, USA. dophinlv@gmail.com.
authors: Yifeng
authors: Y
authors: Lu
authors: Department of Cell Biology, Windber Research Institute, 620 7th Street, Windber, PA, 15963, USA. j.dorchak@wriwindber.org.
authors: Jesse
authors: J
authors: Dorchak
authors: Department of Cell Biology, Windber Research Institute, 620 7th Street, Windber, PA, 15963, USA. r.clancy@wriwindber.org.
authors: Rebecca
authors: R
authors: Clancy
authors: Department of Cell Biology, Windber Research Institute, 620 7th Street, Windber, PA, 15963, USA. j.slavik@wriwindber.org.
authors: Julianna
authors: J
authors: Slavik
authors: Department of Pathology, Uniformed Services University for Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20184, USA. mary.cutler@usuhs.edu.|Murtha Cancer Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA. mary.cutler@usuhs.edu.
authors: Mary Lou
authors: ML
authors: Cutler
authors: Department of Surgery, Walter-Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA. Craig.D.Shriver.mil@health.mil.|Murtha Cancer Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA. Craig.D.Shriver.mil@health.mil.
authors: Craig D
authors: CD
authors: Shriver
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D010655:Phenylenediamines / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D036341:Intercellular Signaling Peptides and Proteins; D010655:Phenylenediamines; D012428:Ruthenium; C034193:1,2-diaminobenzene