当前位置: X-MOL 学术Redox Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Chalcone suppresses tumor growth through NOX4-IRE1α sulfonation-RIDD-miR-23b axis
Redox Biology ( IF 10.7 ) Pub Date : 2021-01-06 , DOI: 10.1016/j.redox.2021.101853
Hyun-Kyoung Kim 1 , Hwa-Young Lee 2 , Thoufiqul Alam Riaz 3 , Kashi Raj Bhattarai 1 , Manoj Chaudhary 3 , Jin Hee Ahn 4 , Jieun Jeong 4 , Hyung-Ryung Kim 5 , Han-Jung Chae 1
Affiliation  

Chalcone is a polyphenolic compound found abundantly in natural plant components. They have been acclaimed as potential antitumor compounds in multiple tumor cells. However, not much attention has been paid to elucidate its antitumor mechanism of action. Here, chalcone was demonstrated to trigger endoplasmic reticulum (ER) stress-induced apoptosis through sulfonation of IRE1α by ER-localized NADPH oxidase 4 (NOX4). IRE1α-sulfonation at a cysteine residue was shown to induce “regulated IRE1α-dependent decay” (RIDD) of mRNA rather than specific splicing of XBP1. The IRE1α sulfonation-induced RIDD degraded miR-23b, enhancing the expression of NOX4. The expression of NOX4 was also upregulated in breast, and prostate cancer tissue. In chalcone-administered mice in vivo, tumor growth was regressed by the consistent mechanisms “NOX4-IRE1α sulfonation-RIDD”. Similarly, NOX4 activation and IRE1α sulfonation were also highly increased under severe ER stress conditions. Together, these findings suggest chalcone as a lead anticancer compound where it acts through NOX4-IRE1α-RIDD-miR-23b axis providing a promising vision of chalcone derivatives’ anticancer mechanism.



中文翻译:

查尔酮通过NOX4-IRE1α磺化-RIDD-miR-23b轴抑制肿瘤的生长

查尔酮是在天然植物成分中大量发现的多酚化合物。它们被认为是多种肿瘤细胞中潜在的抗肿瘤化合物。然而,没有太多的注意力来阐明其抗肿瘤作用机制。在这里,查尔酮被证明可通过ER定位的NADPH氧化酶4(NOX4)磺化IRE1α触发内质网(ER)应激诱导的细胞凋亡。半胱氨酸残基处的IRE1α磺化显示可诱导mRNA的“调节的IRE1α依赖性衰变”(RIDD),而不是XBP1的特异性剪接。IRE1α磺化诱导的RIDD降解了miR-23b,从而增强了NOX4的表达。乳腺癌和前列腺癌组织中NOX4的表达也上调。在体内查尔酮给药的小鼠,通过一致的机制“NOX4-IRE1α磺化-RIDD”使肿瘤生长消退。同样,在严重的内质网应激条件下,NOX4活化和IRE1α磺化也大大增加。总之,这些发现表明查耳酮是一种主要的抗癌化合物,它通过NOX4-IRE1α-RIDD-miR-23b轴起作用,为查耳酮衍生物的抗癌机制提供了广阔前景。

更新日期:2021-01-12
down
wechat
bug