title: The molecular response of vanadium complexes of nicotinoyl hydrazone in cervical cancers--a possible interference with HPV oncogenic markers.
abstract: OBJECTIVE
  Hydrazones belonging to the class of NNO donor Schiff bases are reported to have extensive anti-viral activity and anti-neoplastic activity against certain cancers such as colon cancer, hepatocellular carcinoma and testicular cancer. Here we aim to study the possible effects of two novel nicotinoyl hydrazones on Human papillomavirus (HPV) infected cervical cancers.
  
  
  METHODS
  The effect of vanadium complexes on the proliferation of SiHa and HeLa cells was analyzed using MTT assay. The apoptotic potentials of the complexes were assessed by their ability to induce DNA condensation as well as loss of mitochondrial membrane potential. Caspase activity assay and DNA content analysis were performed to understand the mechanism of apoptotic induction. RT-PCR analysis of cell cycle genes, GADD45, p53, p21 and HPV specific oncogenes, E6 and E7 were used to elucidate the molecular mechanism of the complexes.
  
  
  RESULTS
  OVK 49 exhibits an increased apoptosis inducing potential when compared to OVK 89 in HPV16 positive SiHa cells compared to HPV18 positive HeLa. A down regulation for E6 and E7 mRNA transcripts along with the induction of p53 protein in SiHa cells were observed when treated with OVK 49 indicating that OVK 49 might have promising anti-cancer activity against HPV16 positive cervical cancers.
  
  
  CONCLUSIONS
  This is the first study demonstrating that vanadium complexes could induce a p53 dependent apoptotic mechanism in high risk HPV16-positive cervical cancers.
authors.affiliation: Cancer Research Program 5, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014 Kerala, India.
authors.forename: Rakesh S
authors.initials: RS
authors.lastname: Nair
authors.affiliation: Department of Applied Chemistry, Cochin University of Science & Technology, Kochi 682 022 Kerala, India.
authors.forename: Mini
authors.initials: M
authors.lastname: Kuriakose
authors.affiliation: Cancer Research Program 5, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014 Kerala, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Somasundaram
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research Mohali (IISERM), Punjab, India.
authors.forename: Vinesh
authors.initials: V
authors.lastname: Shenoi
authors.affiliation: Department of Applied Chemistry, Cochin University of Science & Technology, Kochi 682 022 Kerala, India. Electronic address: mrp@cusat.ac.in.
authors.forename: M R Prathapachandra
authors.initials: MR
authors.lastname: Kurup
authors.affiliation: Cancer Research Program 5, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014 Kerala, India. Electronic address: priyasrinivas@rgcb.res.in.
authors.forename: Priya
authors.initials: P
authors.lastname: Srinivas
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014639:Vanadium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014639:Vanadium; D004247:DNA
keywords: HPV16-positive; Nicotinoyl hydrazones; Oxidovanadium; SiHa