title: Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Departments of Obstetrics and Gynecology, University of California Irvine, Orange, CA, USA.
authors.forename: Ramez N
authors.initials: RN
authors.lastname: Eskander
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Randall
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sakai
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Bang
authors.initials: B
authors.lastname: Hoang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives; D000077143:Docetaxel; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D000077022:Survivin; D043823:Taxoids; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D010936:Plant Extracts; D000077022:Survivin; D043823:Taxoids; C452039:flavokawain B; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine