Document Detail


Arsenic trioxide amplifies cisplatin toxicity in human tubular cells transformed by HPV-16 E6/E7 for further therapeutic directions in renal cell carcinoma.
MedLine Citation:
PMID:  25444910     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Human papillomavirus (HPV) DNA integrations may affect therapeutic responses in cancers through ATM network-related DNA damage response (DDR). We studied whether cisplatin-induced DDR was altered in human HK-2 renal tubular cells immortalized by HPV16 E6/E7 genes. Cytotoxicity assays utilized thiazolyl blue dye and DDR was identified by gene expression differences, double-strand DNA breaks, ATM promoter activity, and analysis of cell cycling and side population cells. After cisplatin, HK-2 cells showed greater ATM promoter activity indicating activation of this network, but DDR was muted, since little γH2AX was expressed, DNA strand breaks were absent and cells continued cycling. When HK-2 cells were treated with the MDM2 antagonist inducing p53, nutlin-3, or p53 transcriptional activator, tenovin-1, cell growth decreased but cisplatin toxicity was unaffected. By contrast, arsenic trioxide, which by inhibiting wild-type p53-induced phosphatase-1 that serves responses downstream of p53, and by depolymerizing tubulin, synergistically enhanced cisplatin cytotoxicity including loss of SP cells. Our findings demonstrated that HPV16 E6/E7 altered DDR through p53-mediated cell growth controls, which may be overcome by targeting of WIP1 and other processes, and thus should be relevant for treating renal cell carcinoma.
Authors:
Samriti Dogra; Sriram Bandi; Preeti Viswanathan; Sanjeev Gupta
Publication Detail:
Type:  Journal Article     Date:  2014-11-10
Journal Detail:
Title:  Cancer letters     Volume:  356     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2015 Jan 
Date Detail:
Created Date:  2014-12-08     Completed Date:  -     Revised Date:  2014-12-09    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  953-61     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
P30 CA013330/CA/NCI NIH HHS; P30 DK041296/DK/NIDDK NIH HHS; R01 DK071111/DK/NIDDK NIH HHS; R01 DK088561/DK/NIDDK NIH HHS

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


Previous Document:  MiR-1181 inhibits stem cell-like phenotypes and suppresses SOX2 and STAT3 in human pancreatic cancer...
Next Document:  UNC45A localizes to centrosomes and regulates cancer cell proliferation through ChK1 activation.