title: Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 expression.
abstract: BACKGROUND
  One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities.
  
  
  METHODS
  In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR.
  
  
  RESULTS
  The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G(2)/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1.
  
  
  CONCLUSIONS
  Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality.
authors.affiliation: Department of Biotechnology, Manipal University, PO Box 345050, Dubai, United Arab Emirates.
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Geetganga
authors.initials: G
authors.lastname: Harish
authors.forename: Sathyen Alwin
authors.initials: SA
authors.lastname: Prabhu
authors.forename: Javeria
authors.initials: J
authors.lastname: Mohsin
authors.forename: Munawwar Ali
authors.initials: MA
authors.lastname: Khan
authors.forename: Tahir A
authors.initials: TA
authors.lastname: Rizvi
authors.forename: Chhavi
authors.initials: C
authors.lastname: Sharma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019833:Genistein; D020780:Matrix Metalloproteinase 9