Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines.
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.
Department of Orthopaedic Surgery, University of California Irvine, 101 The City Drive South, Orange, California 92868, USA.
Toshinori
T
Sakai
Ramez N
RN
Eskander
Yi
Y
Guo
Kap Jung
KJ
Kim
Jason
J
Mefford
Justin
J
Hopkins
Nitin N
NN
Bhatia
Xiaolin
X
Zi
Bang H
BH
Hoang
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D002599:Chalcone / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020901:Kava; D008565:Membrane Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077022:Survivin
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C000606775:BCL2L11 protein, human; C107489:BIRC5 protein, human; D000072224:Bcl-2-Like Protein 11; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D000077022:Survivin; C452039:flavokawain B; D002599:Chalcone