Document Detail


Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines.
MedLine Citation:
PMID:  17177841     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The chemical structure of ursolic acid is very similar to that of dexamethasone, a synthetic glucocorticoid. Herein, we investigated the antiproliferative and antiviral effects of ursolic acid and dexamethasone in human papillomavirus (HPV)-associated cervical cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide assay to measure antiproliferative activity, and also characterized apoptosis by DNA fragmentation, 4'-6-diamidino-2-phenylindole (DAPI) staining, and flow cytometry (FACS) analysis. We investigated apoptosis-related proteins using western blots. After in vitro treatment, we used reverse transcription-polymerase chain reaction for the expression of the HPV E6/E7 gene to observe the antiviral effects. Ursolic acid suppressed the growth of HPV-positive cervical carcinoma cells (HeLa, CaSki, and SiHa) in a dose- and time-dependent manner, but not the HPV-negative cervical cancer cell line (C33A). Ursolic acid-treated HeLa cells showed typical apoptosis characteristics in DNA fragmentation, DAPI staining, and FACS analysis. The expression of Fas protein was induced, and caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP) proteins were cleaved after ursolic acid treatment. HPV-18 E6/E7 gene expression decreased after ursolic acid treatment in HeLa cells, but the levels of p53 and Rb proteins did not change. In contrast, dexamethasone, which has a similar structure, did not inhibit proliferation. Our findings may offer new insight into the mechanism of antiproliferative and antiviral effect of ursolic acid. Also, these results suggest that ursolic acid might be a useful anticancer drug in treatment of HPV-associated cervical neoplasia.
Authors:
E-K Yim; M-J Lee; K-H Lee; S-J Um; J-S Park
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of gynecological cancer : official journal of the International Gynecological Cancer Society     Volume:  16     ISSN:  1048-891X     ISO Abbreviation:  Int. J. Gynecol. Cancer     Publication Date:    2006 Nov-Dec
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-02-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111626     Medline TA:  Int J Gynecol Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2023-31     Citation Subset:  IM    
Affiliation:
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, The Catholic University of Korea, Seoul, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  pharmacology,  toxicity
Antiviral Agents / chemistry,  pharmacology*,  toxicity
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dexamethasone / chemistry,  pharmacology*,  toxicity
Female
Humans
Molecular Structure
RNA, Messenger / genetics
Triterpenes / chemistry,  pharmacology*,  toxicity
Uterine Cervical Neoplasms / genetics,  pathology*
Viral Proteins / genetics
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antiviral Agents; 0/RNA, Messenger; 0/Triterpenes; 0/Viral Proteins; 50-02-2/Dexamethasone; 77-52-1/ursolic acid

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