Document Detail

Inhibition of topoisomerase II α activity and induction of apoptosis in mammalian cells by semi-synthetic andrographolide analogues.
MedLine Citation:
PMID:  22899371     Owner:  NLM     Status:  Publisher    
Topoisomerase II α enzyme plays a critical role in DNA replication process. It controls the topologic states of DNA during transcription and is essential for cell proliferation. Human DNA topoisomerase II α (hTopo II α) is a promising chemotherapeutic target for anticancer agents against a variety of cancer types. In the present study, andrographolide and its structurally modified analogues were investigated for their inhibitory activities on hTopo II α enzyme. Five out of nine andrographolide analogues potently reduced hTopo II α activity and inhibited cell proliferation in four mammalian cell lines (Hela, CHO, BCA-1 and HepG2 cells). IC(50) values for cytotoxicity of analogues 3A.1, 3A.2, 3A.3, 1B and 2C were 4 to 7 μM. Structure-activity relationship studies revealed that both core structure of andrographolide and silicon based molecule of functional group were important for the inhibition of hTopo II α activity whereas position C-19 of analogues was required for anti-proliferation. In addition, the analogue 2C at 10 μM concentration inhibited hTopo II α, and induced apoptosis with nuclear fragmentation and formation of apoptotic bodies in HepG2 cells. The analogue 2C may, therefore, have a therapeutic potential as effective anticancer agent targeting the hTopo II α functions.
Jintapat Nateewattana; Rungnapha Saeeng; Sakkasem Kasemsook; Kanoknetr Suksen; Suman Dutta; Surawat Jariyawat; Arthit Chairoungdua; Apichart Suksamrarn; Pawinee Piyachaturawat
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-17
Journal Detail:
Title:  Investigational new drugs     Volume:  -     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  MLH1-silenced and non-silenced subgroups of hypermutated colorectal carcinomas have distinct mutatio...
Next Document:  Statistical methods for assessing interchangeability of biosimilars.