Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines

Toshinori Sakai, Ramez N. Eskander, Yi Guo, Kap Jung Kim, Jason Mefford, Justin Hopkins, Nitin N. Bhatia, Xiaolin Zi, Bang H. Hoang

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis. Treatment with FKB increased caspase 8, 9, and 3/7 activity compared to vehicle-treated controls, indicating that both extrinsic and intrinsic apoptotic pathways were activated. Furthermore, FKB treatment of both cell lines resulted in increased mRNA and protein expression of death receptor-5 and the mitochondrial pro-apoptotic proteins Bim and Puma, while down-regulating the expression of an inhibitor of apoptosis, survivin in a dose-dependent manner. Our results suggest the natural compound FKB has a pro-apoptotic effect on SS cell lines. FKB may be a new chemotherapeutic strategy for patients with SS and deserves further investigation as a potential agent in the treatment of this malignancy.

Original languageEnglish (US)
Pages (from-to)1045-1050
Number of pages6
JournalJournal of Orthopaedic Research
Volume30
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • apoptosis
  • flavokawain
  • synovial sarcoma

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Sakai, T., Eskander, R. N., Guo, Y., Kim, K. J., Mefford, J., Hopkins, J., Bhatia, N. N., Zi, X., & Hoang, B. H. (2012). Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. Journal of Orthopaedic Research, 30(7), 1045-1050. https://doi.org/10.1002/jor.22050