Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors
Authors: Narayanaperumal Pravin
Natarajan Raman
Journal: European Journal of Medicinal Chemistry (2014)
Discipline: CHEMISTRY
Keywords: Antitumor activity; Carboplatin; Cu(II) and Zn(II) metalloinsertors; Cyclobutane-1,1-dicarboxylic acid; Reactive oxygen species.
Affiliations: Research Department of Chemistry, VHNSN College, Virudhunagar 626 001, India. Electronic address: .

Abstract:  A series of carboplatin type Cu(II) and Zn(II) metalloinsertors (1-8) having β-diketone analogues and biologically significant cyclobutane-1,1-dicarboxylic acid have been synthesized and characterized by spectral and analytical methods. The binding and cleavage propensity of these metalloinsertors on DNA and their cytotoxic effects in live cells have been explored. From the gel electrophoresis study, it is observed that the complexes 1-8 cleave pBR322 DNA via a hydrolytic mechanism induced by hydroxyl radical scavengers, DMSO and EtOH as the reactive oxygen species (ROS). In vivo antitumor efficacy has been studied on EAC tumor bearing mice which is assessed by mean survival time, effect on hematological parameters and solid tumor volume. The results strongly support that complex 1 shows potent antitumor effect against EAC and higher than the standard drug carboplatin. Moreover, the cytotoxicity of the complexes, screened on a panel of human cancerous cell lines viz., human cervical cancer cells (HeLa), human breast adenocarcinoma cells (MCF-7), human laryngeal epithelial carcinoma cells (HEp-2), human liver carcinoma cells (Hep G2) and non-cancerous NIH 3T3 mouse embryonic fibroblasts cell lines, reveals that complex 1 exhibits a better anticancer activity than other complexes and standards. 

Retracted: No

PubPeer comments:
 Could the authors comment on what appear to be some repeated features? ![file] , 
 #1 Cells have appeared or disappeared between the two versions of (a). ![file] , 
 Fig. 6.  Agarose gel electrophoresis pattern for the cleavage of pBR322 plasmid DNA (10 mM) by complexes 1-8 at 37 u0004C after incubation for 45 min at 30 mM concentration with histogram of % cleavage forms. lane 1: DNA control; lane 2: (100 mM) CuCl2 + DNA; lane 3: (100 mM) ZnCl2 + DNA; lane 4: complex 1 + DNA; lane 5: complex 2 + DNA; lane 6: complex 3 + DNA. lane 7: complex 4 + DNA; lane 8: complex 5 + DNA; lane 9: complex 6 + DNA; lane 10: complex 7 + DNA; lane 11: complex 8 + DNA. ![file] Fig. 6 from [Pravin et al (2015)] .  Agarose gel electrophoresis pattern for the cleavage of pBR322 plasmid DNA (10 M) by complexes 1u20138 at 37 u25e6C after incubation for 45 min at 25 M concentration with histogram of % cleavage forms; lane 1: DNA control; lane 2: (100 M) CuCl2 + DNA; lane 3: (100 M) ZnCl2 + DNA; lane 4: complex 1 + DNA; lane 5: complex 2 + DNA; lane 6: complex 3 + DNA. Lane 7: complex 4 + DNA; lane 8: complex 5 + DNA; lane 9: complex 6 + DNA; lane 10: complex 7 + DNA; lane 11: complex 8 + DNA. ![file] Fig. 7.  Agarose gel electrophoresis pattern for the cleavage pattern of pBR322 DNA (10 mM) by complexes 1 and 5 at 37 u0004C after incubation for 45 min 30 mM concentration with histogram of % cleavage forms. In absence and presence of complex 1 with different histogram of % cleavage forms. In absence and presence of complex 1 with different activators: lane 1, DNA control; lane 2, DNA + Asc (100 mM); lane 3, DNA + H2O2 (100 mM); lane 4, DNA + GSH (100 mM); lane 5, DNA u00fe MPA (100 mM); lane 6, DNA + 1 + Asc (100 mM); lane 7, DNA + 1 + MPA (100 mM); lane 8, DNA + 1 + GSH (100 mM); lane 9, DNA + 1 + H2O2 (100 mM); lane 10, DNA + 5 + GSH (100 mM); lane 11, DNA + 5 + H2O2 (100 mM); lane 12, DNA + 5 + MPA (100 mM); lane 13, DNA + 5 + AH2 (100 mM). ![file] Fig. 7 from Pravin et al (2015).  Agarose gel electrophoresis pattern for the cleavage pattern of pBR322 DNA (10 M) by complexes 1 and 5 at 37 u25e6C after incubation for 45 min (25 M) concentration with histogram of % cleavage forms. In absence and presence of complex 1 with different activators: lane 1, DNA control; lane 2, DNA+Asc (100 M); lane 3, DNA+ H2O2 (100 M); lane 4, DNA+ GSH (100 M); lane 5, DNA+ MPA (100 M); lane 6, DNA+ 1 +Asc (100 M); lane 7, DNA+ 1 + MPA (100 M); lane 8, DNA+ 1 + GSH (100 M); lane 9, DNA+ 1 + H2O2 (100 M); lane 10, DNA+ 5 + GSH (100 M); lane 11, DNA+ 5 + H2O2 (100 M); lane 12, DNA+ 5 + MPA (100 M); lane 13, DNA+ 5 +AH2 (100 M). ![file] , 
 #2 Fig 1(a): ![file] , 
 #4 Respected and dear sir, Thank you very much for your kind email regarding the paper. We have done the work on similar systems under same conditions. Hence, we are getting the similar results. With your blessings, N.Raman Corresponding Author ,