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

  1. Ramez N. Eskander1,
  2. Leslie M. Randall1,
  3. Toshinori Sakai2,
  4. Yi Guo2,
  5. Bang Hoang2,
  6. Xiaolin Zi3,4,*

Article first published online: 30 APR 2012

DOI: 10.1111/j.1447-0756.2011.01841.x

Issue

Journal of Obstetrics and Gynaecology Research

Journal of Obstetrics and Gynaecology Research

Volume 38, Issue 8, pages 1086–1094, August 2012

Additional Information

How to Cite

Eskander, R. N., Randall, L. M., Sakai, T., Guo, Y., Hoang, B. and Zi, X. (2012), Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line. Journal of Obstetrics and Gynaecology Research, 38: 1086–1094. doi: 10.1111/j.1447-0756.2011.01841.x

Author Information

  1. 1

    Departments of Obstetrics and Gynecology

  2. 2

    Orthopoedic Surgery

  3. 3

    Urology

  4. 4

    Pharmaceutical Sciences, University of California Irvine, Orange, California, USA

*Dr Xiaolin Zi, Department of Urology, University of California Irvine, 101 The City Drive South, Building 55/Room 302, Orange, CA 92868, USA. Email: xzi@uci.edu

Publication History

  1. Issue published online: 24 JUL 2012
  2. Article first published online: 30 APR 2012
  3. Received: June 7 2011.; Accepted: November 25 2011.

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Keywords:

  • apoptosis;
  • cell-cycle arrest;
  • flavokawain B;
  • leiomyosarcoma;
  • uterine cancer

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 IC50 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.

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