Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression

Arif Hussain, Geetganga Harish, Sathyen Alwin Prabhu, Javeria Mohsin, Munawwar Ali Khan, Tahir A. Rizvi, Chhavi Sharma

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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 G2/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1. Conclusion: 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.

Original languageEnglish
Pages (from-to)e387-e393
JournalCancer Epidemiology
Volume36
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Apoptosis
  • Cervical cancer
  • Chemoprevention
  • Genistein
  • Invasion
  • MMP-9
  • TIMP-1

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research

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