Document Detail


Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells.
MedLine Citation:
PMID:  22561209     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50μM) for 24h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.
Authors:
Yu Wang; Qiao Liu; Zhaojian Liu; Boxuan Li; Zhaoliang Sun; Haibin Zhou; Xiyu Zhang; Yaoqin Gong; Changshun Shao
Related Documents :
20118219 - Temporal relationship between primary and motile ciliogenesis in airway epithelial cells.
20111679 - The role of bloom index of gelatin on the interaction with retinal pigment epithelial c...
20843269 - Acute secretory cell toxicity and epithelial exfoliation after smoke inhalation injury ...
9330349 - Dna synthesis, cell proliferation index in normal and abnormal gallbladder epithelium.
3207189 - Electron microscopic studies on the thymus of the arabian camel (camelus dromedarius).
3749149 - Control of lens cell differentiation and ion fluxes by growth factors.
25371289 - Combination of the mtor inhibitor rad001 with temozolomide and radiation effectively in...
7010369 - Studies of the functional role of the intrarenal renin-angiotensin system.
12151309 - Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-26
Journal Detail:
Title:  Mutation research     Volume:  -     ISSN:  0027-5107     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-5-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genomic characterization of seven distinct bat coronaviruses in Kenya.
Next Document:  Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns.