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首页> 外文期刊>Molecular Cancer >Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis
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Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis

机译：Flavokawain B，一种卡瓦查尔酮，通过G2 / M细胞周期阻滞和凋亡抑制人骨肉瘤细胞的生长

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Background Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Limited by the severe toxicity of conventional agents, the therapeutic bottleneck of osteosarcoma still remains unconquered. Flavokawain B (FKB), a kava extract, has been reported to have significant anti-tumor effects on several carcinoma cell lines both in vitro and in vivo . Its efficacy and low toxicity profile make FKB a promising agent for use as a novel chemotherapeutic agent. Results In the current study, we investigated the anti-proliferative and apoptotic effects of FKB against human osteosarcomas. Exposure of OS cells to FKB resulted in apoptosis, evidenced by loss of cell viability, morphological changes and the externalization of phosphatidylserine. Apoptosis induced by FKB resulted in activation of Caspase-3 /7, -8 and ?9 in OS cell lines, 143B and Saos-2. FKB also down-regulated inhibitory apoptotic markers, including Bcl-2 and Survivin and led to concomitant increases in apoptotic proteins, Bax , Puma and Fas. Therefore, the induction of apoptosis by FKB involved both extrinsic and intrinsic pathways. FKB also caused G2/M phase cell cycle arrest, which was observed through reductions in the levels of cyclin B1, cdc2 and cdc25c and increases in Myt1 levels. Furthermore, migration and invasion ability was decreased by FKB in a dose-dependent manner. The cytotoxicity profile showed FKB had significant lower side effects on bone marrow cells and small intestinal epithelial cells compared with Adriamycin. Conclusions Taken together, our evidence of apoptosis and cell cycle arrest by FKB treatment with less toxicity than the standard treatments provides an innovative argument for the use of FKB as a chemotherapeutic and chemopreventive compound. In vivo experiments utilizing FKB to reduce tumorigenesis and metastatic potential will be crucial to further justify clinical application.
机译：背景骨肉瘤（OS）是最常见的原发性骨恶性肿瘤，极易发生局部浸润和远处转移。受常规药物严重毒性的限制，骨肉瘤的治疗瓶颈仍未被克服。 Flavokawain B（FKB），一种卡瓦提取物，据报道在体外和体内对几种癌细胞具有显着的抗肿瘤作用。它的功效和低毒性使FKB成为一种有前途的新型化学治疗剂。结果在本研究中，我们研究了FKB对人骨肉瘤的抗增殖和凋亡作用。 OS细胞暴露于FKB会导致细胞凋亡，这可以通过细胞活力丧失，形态变化和磷脂酰丝氨酸的外部化来证明。由FKB诱导的凋亡导致OS细胞系143B和Saos-2中Caspase-3 / 7，-8和β9的活化。 FKB还下调了抑制性凋亡标志物，包括Bcl-2和Survivin，并导致凋亡蛋白Bax，Puma和Fas随之增加。因此，由FKB诱导的细胞凋亡涉及外在和内在途径。 FKB还引起G2 / M期细胞周期停滞，这是通过降低细胞周期蛋白B1，cdc2和cdc25c的水平并增加Myt1的水平来观察到的。此外，FKB以剂量依赖性方式降低迁移和侵袭能力。细胞毒性概况显示，与阿霉素相比，FKB对骨髓细胞和小肠上皮细胞的副作用明显较低。结论综上所述，我们的证据表明，通过FKB处理所致的凋亡和细胞周期停滞现象，其毒性低于标准治疗方法，为将FKB用作化学治疗和化学预防性化合物提供了创新的论据。利用FKB减少肿瘤发生和转移潜力的体内实验对于进一步证明临床应用至关重要。

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