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Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells.
MedLine Citation:
PMID:  22736505     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Genistein, a soy isoflavone, has been reported to exhibit multiple effects, such as inducing cell cycle arrest, triggering apoptosis, inhibiting the activation of NF(K) B and inactivating several signaling cascades in human cancer cells. In vivo studies demonstrating antiangiogenesis and antimetastatic effects of genistein have also been reported. Here, we demonstrate that genistein inhibits the growth of glioblastoma multiforme and medulloblastoma cells with different TP53 mutations and radio-responses by arresting the cells at G2/M phase of the cell cycle. The cell cycle arrest was found to be independent of DNA damage and such an arrest was sustainable for at least 10 days even after drug removal. Annexin V staining revealed absence of apoptotic or necrotic cell populations after genistein treatment. This supports the observation that genistein induces insignificant DNA damage and indicates that the cell cycle arrest triggered does not lead to cell death. Gene and protein expression studies reveal similar changes in the same pathways following treatment in the cell types tested. Genistein was also able to inhibit telomerase activity resulting in telomere shortening. Thus, we demonstrate, for the first time, that genistein induces growth arrest in association with telomerase inhibition in brain tumor cells via the suppression of TR- and TERT mRNA. By elucidating the mechanisms of anticancer effects after genistein treatment in brain tumor cells, there will be a premise for the incorporation of genistein dietary sources to complement radiotherapy in brain tumor patients. © 2012 Wiley Periodicals, Inc.
Authors:
Aik Kia Khaw; Jacklyn Wei Yan Yong; Guruprasad Kalthur; M Prakash Hande
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-27
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  -     ISSN:  1098-2264     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Physiology, Genome Stability Laboratory, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
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