Berberine Attenuates Cell Motility via Inhibiting Inflammation-Mediated Lysyl Hydroxylase-2 and Glycolysis.
Berberine Attenuates Cell Motility via Inhibiting Inflammation-Mediated Lysyl Hydroxylase-2 and Glycolysis.
复制标题
小檗碱通过抑制炎症介导的赖氨酰羟化酶 2 和糖酵解来减弱细胞活力
DOI：
10.3389/fphar.2022.856777
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
Wei, Xiaohui
中科院分区：
文献类型：
--
作者：
Du, Yishan;Khan, Muhammad;Fang, Nana;Ma, Fang;Du, Hongzhi;Tan, Zhenya;Wang, Hua;Yin, Shi;Wei, Xiaohui
赖氨酰羟基酶-2(LH2)参与胶原沉积过程中端肽赖氨酸残基的羟化。最近的研究表明，慢性炎症性疾病产生的白介素6可能触发LH2的表达，从而加速细胞的运动。小檗碱是从中药黄连中提取的生物碱，在多种疾病中具有潜在的抗炎活性。黄连素的抗炎活性是通过降低促炎细胞因子如IL-6、IL-8和干扰素-γ来证实的。然而，黄连素是否以及如何抑制三阴性乳腺癌(TNBC)的细胞运动抑制转移尚未得到证实，其潜在机制尚不清楚。我们在体外研究了黄连素对炎性细胞因子分泌、细胞增殖和迁移的影响，并进一步探讨了黄连素对体内生长和转移的影响。黄连素以剂量依赖的方式抑制TNBC细胞的增殖、运动和糖酵解过程。黄连素可抑制TNBC细胞分泌IL-6，并抑制IL-6刺激的细胞迁移。从机制上讲，黄连素显著抑制LH2在mRNA和蛋白质水平的表达。LH2耗竭导致黄连素的抗动作用减弱，这种现象与LH2抑制后的糖酵解抑制有关。反之，异位修复LH2可进一步增强黄连素的抗动作用。此外，黄连素在体内被证实能抑制细胞的生长和运动，在体内也能抑制LH2和糖酵解酶的表达。综上所述，本研究表明黄连素可能通过调节TNBC的LH2而成为一种有前景的治疗药物。
Lysyl hydroxylase-2 (LH2) involves in the hydroxylation of telopeptide lysine residues during collagen deposition. Recent studies indicate that interleukin (IL)-6 generated by the chronic inflammation disease may trigger the LH2 expression to accelerate cell motility. Berberine is the alkaloid derived from the traditional Chinese medicine Coptis chinensis, which displays potential anti-inflammatory activity in multiple diseases. The anti-inflammatory activity of berberine has been confirmed by reducing proinflammatory cytokines such as IL-6, IL-8, and IFN-γ. However, whether and how berberine inhibits cellular motility against metastatic spread in triple-negative breast cancer (TNBC) has not been demonstrated, and the underlying mechanism remains unclear. We investigated the effects of berberine on the inflammatory cytokine secretion, cell proliferation, and migration in vitro and further explored the effect of berberine on growth and metastasis in vivo. Berberine restrained TNBC cell proliferation, motility, and glycolysis process in a dose-dependent way. The secretion of IL-6 was abrogated by berberine in TNBC cells, and IL-6-stimulated cell migration was inhibited by berberine. Mechanistically, berberine remarkably suppressed LH2 expression at both mRNA and protein levels. LH2 depletion led to decreasing the antimotility effect of berberine, and this phenomenon was related to the suppressed glycolysis after LH2 inhibition. Conversely, ectopic restoration of LH2 could further increase the antimotility effect of berberine. Moreover, berberine was confirmed to inhibit cell growth and motility in vivo, and the expression of LH2 and glycolytic enzymes was also blocked by berberine in vivo. Collectively, this study indicated that berberine could be a promising therapeutic drug via regulating LH2 for TNBC.
登录
查看更多内容
影响因子：
5.5
作者：
Qi Y;Xu R
通讯作者：
Xu R
影响因子：
2.9
作者：
Du, Wenwu;Liu, Ning;He, Yi
通讯作者：
He, Yi
影响因子：
4.4
作者：
Liu, Jingjing;Luo, Xialin;Lu, Haitao
通讯作者：
Lu, Haitao
脂肪细胞来源的 IL-6 和瘦素通过上调 Lysyl Hydroxylase-2 表达促进乳腺癌转移。
影响因子：
8.4
作者：
He, Jin-Yong;Wei, Xiao-Hui;Sun, Li
通讯作者：
Sun, Li
DOI：
10.1016/j.bbadis.2020.165897
发表时间：
2020-11-01
影响因子：
6.2
作者：
Ponnusamy, Lavanya;Kothandan, Gugan;Manoharan, Ravi
通讯作者：
Manoharan, Ravi