Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3.

Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3.
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Bavachin 通过抑制核因子 kappa B 以及信号转导子和转录激活子 3 的激活来诱导多发性骨髓瘤细胞系凋亡。

DOI:
10.1016/j.biopha.2018.02.019
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发表时间:
2018
期刊:
Biomed Pharmacother.
影响因子:
--
通讯作者:
Nishida S.
Nishida S.
中科院分区:
--
文献类型:
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作者:
Takeda T;Tsubaki M;Tomonari Y;Kawashima K;Itoh T;Imano M;Satou T;Nishida S.

文献摘要

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巴伐辛是一种从天然草本植物如补骨脂中纯化的植物雌激素。在这项研究中,我们检测了巴伐辛在多发性骨髓瘤(MM)细胞系中的作用。我们发现,巴伐辛降低了MM细胞系的活力,但对正常细胞没有细胞毒性。抑制核因子κB (NF-κB)和转录信号传导激活因子3 (STAT3)的激活。此外,巴伐辛增加了p53和NOXA的表达,降低了X-linked inhibitor of apoptosis protein (XIAP)、survivin、B细胞淋巴瘤-extra large (Bcl-xL)和Bcl-2的表达。此外,bavachin通过激活caspase-3和caspase-9诱导细胞凋亡,暗示参与了线粒体途径。我们的研究结果表明,巴伐青素通过抑制NF-κB和STAT3的激活诱导MM细胞株凋亡。最重要的是,目前很少有高效、特异性和安全性高的NF-κB和STAT3抑制剂可用于临床癌症治疗。因此,靶向NF-κB和STAT3的bavachin是治疗MM的潜在抗癌药物。
Bavachin is a phytoestrogen purified from natural herbal plants such as Psoralea corylifolia. In this study, we examined the effect of bavachin in multiple myeloma (MM) cell lines. We found that bavachin decreased the viability of MM cell lines, but was not cytotoxic towards normal cells. It inhibited the activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Furthermore, bavachin increased the expression of p53 and NOXA, and decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, B cell lymphoma-extra large (Bcl-xL), and Bcl-2. Additionally, bavachin induced apoptosis by the activation of caspase-3 and caspase-9, implicating the involvement of the mitochondrial pathway. Our results suggest that bavachin induces apoptosis through the inhibition of NF-κB and STAT3 activation in MM cell lines. Most importantly, few NF-κB and STAT3 inhibitors with high efficiency, specificity, and safety are currently available for clinical cancer therapy. Hence, bavachin, which targets NF-κB and STAT3, is a potential anticancer agent for the treatment of MM.