The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis,Phytomedicine

当前位置： X-MOL 学术 › Phytomedicine › 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.)

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis
Phytomedicine ( IF 6.7 ) Pub Date : 2024-05-12 , DOI: 10.1016/j.phymed.2024.155734
Jin-Quan Zhao ₁ , Qi-Qi Zhou ₁ , Yuan Sun ₁ , Ting Yu ₁ , Yan Jiang ₂ , Hui-Jun Li ₁

Affiliation

Toxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. To evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. The effect of DIOB on NSCLCL was evaluated through CCK8, colony formation, and flow cytometry. The efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. DIOB effectively hindered the progression of NSCLC both and settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. For the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

中文翻译：

Diosbulbin B 的抗非小细胞肺癌作用：靶向 YY1 诱导的细胞周期阻滞和凋亡

有毒成分经常表现出独特的特性和活性，为抗癌药物的发展提供了充足的机会。作为 L. (DB) 的主要肝毒性成分，Diosbulbin B (DIOB) 因其无毒剂量的抗肿瘤活性而被广泛研究。然而，DIOB对抗非小细胞肺癌（NSCLC）的有效性和机制仍不清楚。评价DIOB的抗NSCLC活性并阐明其具体作用机制。通过 CCK8、集落形成和流式细胞术评估 DIOB 对 NSCLCL 的影响。采用HE染色、tunel染色、免疫组化、生化指标检测等多种技术评估DIOB治疗NSCLC的疗效和安全性。为了了解潜在的机制，采用细胞转染、蛋白质印迹、分子对接、细胞热位移测定（CESTA）和表面等离子共振（SPR）进行研究。 DIOB 在未观察到不良效应浓度 (NOAEC) 和安全剂量的情况下均有效阻碍了 NSCLC 的进展。具体而言，DIOB 诱导 A549、PC-9 和 H1299 细胞显着的 G0/G1 期阻滞和细胞凋亡，同时还显着抑制裸鼠皮下肿瘤的生长。从机制上讲，DIOB可以直接与癌基因阴阳1（YY1）相互作用并抑制其表达。 YY1的减少导致抑癌基因P53的触发，通过抑制Cyclin A2、B2、CDK1、CDK2、CDK4、BCL-2的表达以及诱导BAX的表达，诱导NSCLC细胞的细胞周期停滞和凋亡。。在 NSCLC 细胞中，当 YY1 过表达或 P53 被敲低时，DIOB 诱导的 G0/G1 期停滞和细胞凋亡被有效逆转。重要的是，我们观察到 DIOB 通过直接影响 YY1 调节的 c-Myc 和 BIM 的表达而发挥相同的作用，特别是在 P53 缺失的情况下。在首次调查中，这项研究揭示了 DIOB 的抗 NSCLC 作用及其基本机制。由于 DIOB 在对抗 NSCLC 方面具有令人印象深刻的功效，因此已显示出作为 NSCLC 治疗剂的潜力。

更新日期：2024-05-12

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南