Document Detail


Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line.
MedLine Citation:
PMID:  22540374     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To examine the effects of flavokawain B (FKB), a novel kava chalcone, on the growth of uterine leiomyosarcoma (LMS) cells and investigated its utility in the treatment of uterine LMS.
MATERIAL AND METHODS: Uterine leiomyosarcoma (SK-LMS-1), endometrial adenocarcinoma (ECC-1) and the non-malignant, human endometrium fibroblast-like (T-HESC) cell lines were cultured and treated with different concentrations of FKB. Cell viability was determined by MTT assays and the IC(50) was estimated. Fluorescent-activated cell sorting (FACS) analysis of apoptosis and cell cycle was performed. Real-time reverse-transcription polymerase chain reaction and western blot analysis were utilized to evaluate differences in the expression of apoptotic markers.
RESULTS: FKB preferentially inhibited the growth of SK-LMS-1 and ECC-1 cells compared to T-HESC control cells. FKB significantly increased both early and late apoptosis in SK-LMS-1 and ECC-1 cells relative to control. Cell cycle analysis illustrated an increase in the G2/M fraction in treated cell lines relative to control. Furthermore, FKB induced the expression of pro-apoptotic death receptor 5 (DR5), Bim, and Puma, and decreased expression of an inhibitor of apoptosis, survivin. FKB also acted synergistically when combined with docetaxel and gemcitabine (combination index = 0.260).
CONCLUSION: FKB treatment results in cell cycle arrest and a robust induction of apoptosis in SK-LMS-1 and ECC-1 cell lines. This natural product deserved further investigation as a potential therapeutic agent in the treatment of uterine LMS.
Authors:
Ramez N Eskander; Leslie M Randall; Toshinori Sakai; Yi Guo; Bang Hoang; Xiaolin Zi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-30
Journal Detail:
Title:  The journal of obstetrics and gynaecology research     Volume:  38     ISSN:  1447-0756     ISO Abbreviation:  J. Obstet. Gynaecol. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-25     Completed Date:  2012-12-11     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9612761     Medline TA:  J Obstet Gynaecol Res     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1086-94     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents
Apoptosis / drug effects*
Cell Line, Tumor
Deoxycytidine / analogs & derivatives
Drug Evaluation, Preclinical
Drug Synergism
Female
Fibroblasts / drug effects
Flavonoids / pharmacology,  therapeutic use*
G2 Phase Cell Cycle Checkpoints / drug effects*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Inhibitor of Apoptosis Proteins / metabolism
Leiomyosarcoma / drug therapy*,  metabolism
Phytotherapy
Plant Extracts / pharmacology,  therapeutic use
Taxoids
Uterine Neoplasms / drug therapy*,  metabolism
Grant Support
ID/Acronym/Agency:
CA122558/CA/NCI NIH HHS; CA62203/CA/NCI NIH HHS; P30 CA062203/CA/NCI NIH HHS; R01 CA122558/CA/NCI NIH HHS; R01 CA122558-04/CA/NCI NIH HHS; R01 CA122558-04S1/CA/NCI NIH HHS; R21 CA152804/CA/NCI NIH HHS; R21 CA152804-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BIRC5 protein, human; 0/Flavonoids; 0/Inhibitor of Apoptosis Proteins; 0/Plant Extracts; 0/Taxoids; 0/flavokawain B; 0W860991D6/Deoxycytidine; 15H5577CQD/docetaxel; B76N6SBZ8R/gemcitabine
Comments/Corrections

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