Premium
Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line
Author(s) -
Eskander Ramez N.,
Randall Leslie M.,
Sakai Toshinori,
Guo Yi,
Hoang Bang,
Zi Xiaolin
Publication year - 2012
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/j.1447-0756.2011.01841.x
Subject(s) - apoptosis , cell cycle , cell cycle checkpoint , survivin , viability assay , g1 phase , cell growth , cell culture , cancer research , programmed cell death , andrology , chemistry , biology , medicine , biochemistry , genetics
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.