A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization

被引：2

作者：

Tian, Yingying ^{[1
]}

Yang, Ailin ^{[1
]}

Huang, Huiming ^{[1
]}

Xie, Jinxin ^{[1
]}

Wang, Longyan ^{[1
]}

Liu, Dongxiao ^{[1
]}

Wei, Xuejiao ^{[1
]}

Tan, Peng ^{[1
]}

Tu, Pengfei ^{[1
]}

Fu, Dongjun ^{[2
,3
]}

Hu, Zhongdong ^{[2
,3
]}

机构：

[1] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China

[2] Beijing Univ Chinese Med, Beijing Res Inst Chinese Med, Beijing 100029, Peoples R China

[3] 11 North 3rd Ring East Rd, Beijing 100029, Peoples R China

来源：

ARABIAN JOURNAL OF CHEMISTRY | 2024年 / 17卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Pyrrolidine-25-dione derivative; Hepatocellular carcinoma; Proliferation; G2/M phase arrest; Apoptosis; Tubulin polymerization; MICROTUBULE; BINDING; AGENTS;

D O I：

10.1016/j.arabjc.2023.105550

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti-HCC activity (IC50 value of 2.082 mu M) against human HCC HepG2 cells. Moreover, compound 8 significantly suppressed the HepG2 cell multiplication, and triggered G2/M phase arrest of HepG2 cells and their apoptosis. Further mechanistic investigations revealed that compound 8 suppressed tubulin polymerization by directly binding to the colchicine binding site of beta-tubulin. Additionally, compound 8 significantly inhibited tumor growth with low toxicity in nude HepG2 tumor-bearing mice, achieving an approximate inhibition rate of 45.73 %. Therefore, compound 8 represents a promising pharmaceutical candidate for HCC management.

引用

页数：9

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