Document Detail


Polo-like kinase1 (Plk1) knockdown enhances cisplatin chemosensitivity via up-regulation of p73α in p53 mutant human epidermoid squamous carcinoma cells.
MedLine Citation:
PMID:  20655883     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polo-like kinase 1 (Plk1), a critical regulator of mitotic entry, progression and exit, has been shown to be involved in a variety of cancers and thus is becoming an attractive target for cancer management. In case of DNA damage, Plk1 not only inhibits p53 independent apoptosis by dysfunctioning p73α but also allows cells to recover from growth arrest. Here, we showed the effects of knocking down plk1 gene through small interference RNA (siRNA) on cell cycle progression, proliferation and chemosensitivity of p53 mutant A431 cells to cisplatin (CDDP). The expression of Plk1 was measured by RT-PCR and Western blotting. Anti-proliferative response accompanied with cell cycle arrest in G(2)/M phase and induction of cell death was recorded following Plk1 knockdown. Furthermore, cells following knockdown of Plk1, which induced increase of Cyclin B1, p-Cdc2 and p73α with a decrease in p-Cdc25C, were more sensitive to CDDP. CDDP treatment induced nuclear translocation and co-localization of Plk1 with p73α whereas combination of CDDP and Plk1siRNA upregulated the expression of p73α protein in a synergistic manner thereby leading to an increase up to ∼5 folds in CDDP-induced cell death. The increase in caspase-3 activity indicated apoptosis as a contributor in the total cell death. Conclusively, plk1 gene silencing can enhance the sensitivity of A431 cells to low doses of CDDP by upregulating p73α expression and thus can be a revolutionary approach in cancer chemotherapy.
Authors:
Shilpa Tyagi; Kulpreet Bhui; Richa Singh; Madhulika Singh; Sheikh Raisuddin; Yogeshwer Shukla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-22
Journal Detail:
Title:  Biochemical pharmacology     Volume:  80     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2010-10-06     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1326-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Indian Institute of Toxicology Research, Council of Scientific & Industrial Research, Mahatma Gandhi Marg, Lucknow, U.P., India. shilpa_tyagi2000@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Carcinoma, Squamous Cell / drug therapy*,  pathology
Cell Cycle Proteins / antagonists & inhibitors,  genetics,  physiology*
Cell Line, Tumor
Cell Proliferation
Cisplatin / pharmacology*
DNA-Binding Proteins / physiology*
Genes, p53*
Humans
Mutation*
Nuclear Proteins / physiology*
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  genetics,  physiology*
Proto-Oncogene Proteins / antagonists & inhibitors,  genetics,  physiology*
RNA Interference
Tumor Suppressor Proteins / physiology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 0/tumor suppressor protein p73; 15663-27-1/Cisplatin; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1

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