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

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.