College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Biomolecules. 2019 Jul 7;9(7):262. doi: 10.3390/biom9070262.
Here, we determined the anti-neoplastic actions of formononetin (FT) against multiple myeloma (MM) and elucidated its possible mode of action. It was observed that FT enhanced the apoptosis caused by bortezomib (Bor) and mitigated proliferation in MM cells, and these events are regulated by nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and activator protein-1 (AP-1) activation. We further noted that FT treatment reduced the levels of diverse tumorigenic proteins involved in myeloma progression and survival. Interestingly, we observed that FT also blocked persistent NF-κB, PI3K/AKT, and AP-1 activation in myeloma cells. FT suppressed the activation of these oncogenic cascades by affecting a number of signaling molecules involved in their cellular regulation. In addition, FT augmented tumor growth-inhibitory potential of Bor in MM preclinical mouse model. Thus, FT can be employed with proteasomal inhibitors for myeloma therapy by regulating the activation of diverse oncogenic transcription factors involved in myeloma growth.
在这里，我们确定芒柄花素（FT）对多发性骨髓瘤（MM）的抗肿瘤作用，并阐明其可能的作用模式。结果表明，FT 增强硼替佐米（Bor）引起的细胞凋亡并减轻 MM 细胞的增殖，这些事件受核因子-κB（NF-κB）、磷脂酰肌醇 3-激酶（PI3K）/AKT 和激活蛋白-1（AP-1）的激活调节。我们进一步注意到，FT 处理降低了与骨髓瘤进展和存活相关的多种致瘤蛋白的水平。有趣的是，我们观察到 FT 还阻止了骨髓瘤细胞中持续的 NF-κB、PI3K/AKT 和 AP-1 的激活。FT 通过影响参与其细胞调节的许多信号分子来抑制这些致癌级联的激活。此外，FT 增强了硼替佐米在 MM 临床前小鼠模型中的肿瘤生长抑制潜力。因此，FT 可以通过调节参与骨髓瘤生长的多种致癌转录因子的激活与蛋白酶体抑制剂联合用于骨髓瘤治疗。
