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

Ramez N. Eskander, Leslie M. Randall, Toshinori Sakai, Yi Guo, Bang H. Hoang, Xiaolin Zi

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 cyclewas performed. Real-Time reversetranscription 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.

Original languageEnglish (US)
Pages (from-to)1086-1094
Number of pages9
JournalJournal of Obstetrics and Gynaecology Research
Volume38
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Chalcone
Leiomyosarcoma
Apoptosis
docetaxel
gemcitabine
Cell Line
Kava
Puma
TNF-Related Apoptosis-Inducing Ligand Receptors
flavokawain B
Growth
Endometrium
Cell Cycle Checkpoints
Biological Products
Inhibitory Concentration 50
Real-Time Polymerase Chain Reaction
Cell Survival
Cell Cycle
Adenocarcinoma
Fibroblasts

Keywords

  • Apoptosis
  • Cell-cycle arrest
  • Flavokawain B
  • Leiomyosarcoma
  • Uterine cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell linejog. / Eskander, Ramez N.; Randall, Leslie M.; Sakai, Toshinori; Guo, Yi; Hoang, Bang H.; Zi, Xiaolin.

In: Journal of Obstetrics and Gynaecology Research, Vol. 38, No. 8, 08.2012, p. 1086-1094.

Research output: Contribution to journalArticle

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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 cyclewas performed. Real-Time reversetranscription 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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AU - Eskander, Ramez N.

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AU - Sakai, Toshinori

AU - Guo, Yi

AU - Hoang, Bang H.

AU - Zi, Xiaolin

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N2 - 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 cyclewas performed. Real-Time reversetranscription 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.

AB - 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 cyclewas performed. Real-Time reversetranscription 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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