p53介导的细胞周期调控是大黄素抑制骨肉瘤细胞的一种潜在机制。

The p53-mediated cell cycle regulation is a potential mechanism for emodin-suppressing osteosarcoma cells.

作者信息

Zhang Qian, Hao Shuli, Wei Guangyou, Liu Xiangyu, Miao Yang

机构信息

Department of Pharmacy, Bozhou People's Hospital, Bozhou, 236800, Anhui Province, China.

Department of Stomatology, Bozhou People's Hospital, Bozhou, 236800, Anhui Province, China.

出版信息

Heliyon. 2024 Feb 23;10(5):e26850. doi: 10.1016/j.heliyon.2024.e26850. eCollection 2024 Mar 15.

DOI:10.1016/j.heliyon.2024.e26850

PMID:38495151

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10943350/

Abstract

BACKGROUND

As the most common primary bone cancer, the therapy of osteosarcoma requires further study. An anthraquinone derivative, emodin, has been found to have anticancer potential. We proposed that emodin suppresses osteosarcoma by cell cycle regulation mediated by p53.

METHODS

This study determined the effect of emodin on viability and apoptosis of 6 osteosarcoma cell lines (p53 null cells MG63, G292, and A-673; p53 mutated cells HOS and SK-PN-DW; p53 expressing cells U2OS and 2 osteoblast cell lines), then knockdown p53 in U2OS, and observed the impacts of emodin on p53, p21, cyclin proteins, and cell cycle.

RESULTS

High dose emodin (40-160 μM) induced cell death and apoptosis of all the cell lines; medium dose emodin (20 μM) preferentially inhibited osteosarcoma cells; low dose emodin (1-10 μM) preferentially inhibited p53 expressing osteosarcoma cells. Emodin dose-dependently inhibited p53 and p21 in U2OS. Emodin at 10 μM decreased the expression of Cdk2, E2F, and Cdk1; and increased RB but had no effects on cyclin E and cyclin B. The knockdown of p53 almost eliminated all the impacts of 10 μM emodin on cell cycle proteins.

CONCLUSIONS

Emodin suppresses U2OS by p53-mediated cell cycle regulation.

摘要

背景

骨肉瘤作为最常见的原发性骨癌，其治疗方法仍需进一步研究。一种蒽醌衍生物，大黄素，已被发现具有抗癌潜力。我们提出大黄素通过p53介导的细胞周期调控来抑制骨肉瘤。

方法

本研究确定了大黄素对6种骨肉瘤细胞系（p53缺失细胞MG63、G292和A - 673；p53突变细胞HOS和SK - PN - DW；p53表达细胞U2OS以及2种成骨细胞系）活力和凋亡的影响，然后在U2OS细胞中敲低p53，并观察大黄素对p53、p21、细胞周期蛋白以及细胞周期的影响。

结果

高剂量大黄素（40 - 160μM）诱导所有细胞系发生细胞死亡和凋亡；中剂量大黄素（20μM）优先抑制骨肉瘤细胞；低剂量大黄素（1 - 10μM）优先抑制p53表达的骨肉瘤细胞。大黄素在U2OS细胞中呈剂量依赖性抑制p53和p21。10μM大黄素可降低Cdk2、E2F和Cdk1的表达；增加RB的表达，但对细胞周期蛋白E和细胞周期蛋白B无影响。敲低p53几乎消除了10μM大黄素对细胞周期蛋白的所有影响。