PMID- 27273962
OWN - NLM
STAT- MEDLINE
DCOM- 20160701
LR  - 20160609
IS  - 1107-0625 (Print)
IS  - 1107-0625 (Linking)
VI  - 21
IP  - 2
DP  - 2016 Mar-Apr
TI  - Anticancer activity of two ruthenium(II)-DMSO-chalcone complexes: Comparison of 
      cytotoxic, pro-apoptotic and antimetastatic potential.
PG  - 482-90
AB  - PURPOSE: Recently, we reported the synthesis and characterization of two 
      complexes of general formula cis-[Ru(S-DMSO)3(R-CO-CH=CH-R')Cl] (R = 
      2-hydroxyphenyl for both, R' = thiophene (1), 3-methyl thiophene (2)) that showed 
      remarkable topoisomerase II inhibition and strong binding with DNA. The aim of 
      this study was the investigation of cytotoxic properties of these complexes 
      against a panel of human tumor cell lines, with elucidation of their anticancer 
      mechanisms in HeLa cells. METHODS: Characterization of anticancer activity of the 
      investigated ruthenium complexes 1 and 2 included analysis of cytotoxicity by MTT 
      assay. Cell cycle phase disruption of HeLa cells treated with complexes 1 and 2 
      was analyzed by flow cytometry after propidium iodide (PI) staining. Annexin 
      V-FITC/PI double staining and further flow cytometry analysis and acridine orange 
      (AO)/ethidium bromide (EB) double staining and fluorescent microscopy were used 
      to determine the apoptotic potential of the investigated ruthenium complexes. The 
      inhibitory effect on gelatinases (MMP-2 and MMP-9) as an indication of possible 
      antimetastatic potential was also analyzed using gelatine zymography. RESULTS: 
      The 50% cell growth inhibition (IC50) values of the investigated complexes ranged 
      between 22.9 and 76.8 muM, with complex 2 being more cytotoxic. Both complexes 
      induced G2 phase cell cycle arrest and apoptosis in HeLa cells. Inhibitory effect 
      of complex 2 on MMP-2 activity was detected. CONCLUSIONS: This work revealed the 
      potential of the investigated Ru(II)-DMSO-chalcone complexes as anticancer agents 
      with cytotoxic and pro-apoptotic activity and indicated complex 2 as leading 
      compound for further chemical modifications and anticancer research.
FAU - Jovanovic, Katarina K
AU  - Jovanovic KK
AD  - Laboratory for Experimental Pharmacology, Department of Experimental Oncology, 
      Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, 
      Serbia.
FAU - Gligorijevic, Nevenka
AU  - Gligorijevic N
FAU - Gaur, Ruchi
AU  - Gaur R
FAU - Mishra, Lallan
AU  - Mishra L
FAU - Radulovic, Sinisa
AU  - Radulovic S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Cyprus
TA  - J BUON
JT  - Journal of B.U.ON. : official journal of the Balkan Union of Oncology
JID - 100883428
RN  - 0 (Chalcones)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Ruthenium Compounds)
RN  - 0 (Topoisomerase II Inhibitors)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Chalcones/chemical synthesis/*pharmacology
MH  - Dimethyl Sulfoxide/analogs & derivatives/chemical synthesis/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase Inhibitors/pharmacology
MH  - Molecular Structure
MH  - Neoplasm Invasiveness
MH  - Neoplasms/*drug therapy/pathology
MH  - Ruthenium Compounds/chemical synthesis/*pharmacology
MH  - Structure-Activity Relationship
MH  - Time Factors
MH  - Topoisomerase II Inhibitors/chemical synthesis/*pharmacology
EDAT- 2016/06/09 06:00
MHDA- 2016/07/02 06:00
CRDT- 2016/06/09 06:00
PHST- 2016/06/09 06:00 [entrez]
PHST- 2016/06/09 06:00 [pubmed]
PHST- 2016/07/02 06:00 [medline]
PST - ppublish
SO  - J BUON. 2016 Mar-Apr;21(2):482-90.