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红秋葵荚乙醇提取物通过破坏结肠癌细胞中的Wnt信号通路诱导异常纺锤体分离和凋亡性细胞死亡。

Ethanolic Extract of Red Okra Pods Induces Aberrant Spindle Segregation and Apoptotic Cell Death by Disrupting the Wnt Signaling Pathway in Colon Cancer Cells.

作者信息

Dewi Firli Rahmah Primula, Wahyuningsih Sri Puji Astuti, Lim Vuanghao, In Lionel Lian Aun, Hayati Alfiah

机构信息

Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.

出版信息

Iran J Med Sci. 2024 Dec 1;49(12):785-793. doi: 10.30476/IJMS.2024.99450.3149. eCollection 2024 Dec.

Abstract

BACKGROUND

In approximately 80% of colorectal cancer cases, mutations in the adenomatous polyposis coli () gene disrupt the Wingless-related integration site (Wnt)/β-catenin signaling pathway, a crucial factor in carcinogenesis. This disruption may result in consequences such as aberrant spindle segregation and mitotic catastrophe. This study aimed to analyze the effectiveness of the ethanolic extract of red okra () pods (EEROP) in inducing apoptosis in colorectal cancer cells (SW480) by inhibiting the Wnt/β-catenin signaling pathway.

METHODS

The IC of EEROP in SW480 cells was determined by treating the cells with varying doses of EEROP, ranging from 0 to 1000 µg/mL. Apoptosis assay and signaling pathway analysis were performed through immunofluorescence staining and Western Blotting on SW480 cells treated with 250 µg/mL of EEROP for 72 hours.

RESULTS

EEROP treatment induced apoptosis in SW480 cells, marked by elevated levels of active caspase-3 (P<0.001) and cleaved poly-(ADP-ribose) polymerase (PARP)-1. Moreover, it notably decreased β-catenin protein levels, resulting in an augmented occurrence of cells displaying abnormal spindle segregation during mitosis (P=0.04).

CONCLUSION

EEROP treatment reduces β-catenin protein levels, promotes abnormal spindle apparatus segregation, and finally leads to apoptotic cell death in CRC cells.

摘要

背景

在大约80%的结直肠癌病例中,腺瘤性息肉病 coli()基因的突变会破坏无翅相关整合位点(Wnt)/β-连环蛋白信号通路,这是致癌过程中的一个关键因素。这种破坏可能导致诸如异常纺锤体分离和有丝分裂灾难等后果。本研究旨在分析红秋葵()豆荚乙醇提取物(EEROP)通过抑制Wnt/β-连环蛋白信号通路诱导结直肠癌细胞(SW480)凋亡的有效性。

方法

通过用0至1000μg/mL不同剂量的EEROP处理SW480细胞来确定EEROP在SW480细胞中的半数抑制浓度(IC)。对用250μg/mL EEROP处理72小时的SW480细胞进行免疫荧光染色和蛋白质印迹法,以进行凋亡检测和信号通路分析。

结果

EEROP处理诱导SW480细胞凋亡,表现为活性半胱天冬酶-3水平升高(P<0.001)和多聚(ADP-核糖)聚合酶-1(PARP-1)裂解增加。此外,它显著降低β-连环蛋白蛋白水平,导致有丝分裂期间显示异常纺锤体分离的细胞发生率增加(P=0.04)。

结论

EEROP处理降低β-连环蛋白蛋白水平,促进异常纺锤体装置分离,最终导致结直肠癌细胞凋亡死亡。

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