title: Apoptosis-inducing Effect of a Palladium(II) Complex-[PdCl(terpy)](sac).2H2O] on Ehrlich Ascites Carcinoma (EAC) in Mice.
abstract: OBJECTIVE
  New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2"-terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo.
  
  
  METHODS
  42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3β, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis.
  
  
  RESULTS
  Expression of p53, PCNA, Bcl-2 was found decreased (p<0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p<0.001) in all groups. The survival-related markers did not show any statistical difference in complex groups.
  
  
  CONCLUSIONS
  The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel.
authors.affiliation: Department of Histology and Embryology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Elif I
authors.initials: EI
authors.lastname: Ikitimur-Armutak
authors.affiliation: Department of Medical Biochemistry, Medical School, Uludag University, Bursa, Turkey.
authors.forename: Engin
authors.initials: E
authors.lastname: Ulukaya
authors.affiliation: Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Gurel-Gurevin
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
authors.affiliation: Department of Medical Biochemistry, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Isbilen-Basok
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gulbin
authors.initials: G
authors.lastname: Sennazli
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gulay
authors.initials: G
authors.lastname: Yuzbasioglu-Ozturk
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Kivilcim
authors.initials: K
authors.lastname: Sonmez
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Faruk
authors.initials: F
authors.lastname: Celik
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Kucukhuseyin
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gurbet
authors.initials: G
authors.lastname: Korkmaz
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Uludag University, Bursa, Turkey.
authors.forename: Veysel T
authors.initials: VT
authors.lastname: Yilmaz
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey umz67@yahoo.com.
authors.forename: Sakir Umit
authors.initials: SU
authors.lastname: Zeybek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D010165:Palladium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D056831:Coordination Complexes; D010165:Palladium; D002945:Cisplatin
keywords: EAC; Pd(II) complex; apoptosis; breast cancer; in vivo