Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line

J Obstet Gynaecol Res. 2012 Aug;38(8):1086-94. doi: 10.1111/j.1447-0756.2011.01841.x. Epub 2012 Apr 30.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Female
  • Fibroblasts / drug effects
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Survivin
  • Taxoids
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Flavonoids
  • Inhibitor of Apoptosis Proteins
  • Plant Extracts
  • Survivin
  • Taxoids
  • flavokawain B
  • Deoxycytidine
  • Docetaxel
  • gemcitabine