Induction of cell death and modulation of Annexin A1 by phytoestrogens in human leukemic cell lines,Saudi Pharmaceutical Journal

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Induction of cell death and modulation of Annexin A1 by phytoestrogens in human leukemic cell lines
Saudi Pharmaceutical Journal ( IF 3.0 ) Pub Date : 2020-12-22 , DOI: 10.1016/j.jsps.2020.12.011
Affidah Sabran ₁ , Endang Kumolosasi ₁ , Ibrahim Jantan ₂ , Jamia Azdina Jamal ₁ , Norazrina Azmi ₁ , Malina Jasamai ₁

Affiliation

Background

Phytoestrogens are polyphenolic plant compounds which are structurally similar to the endogenous mammalian estrogen, 17β-estradiol. Annexin A1 (ANXA1) is an endogenous protein which inhibits cyclo-oxygenase 2 (COX-2) and phospholipase A2, signal transduction, DNA replication, cell transformation, and mediation of apoptosis.

Objective

This study aimed to determine the effects of selected phytoestrogens on annexin A1 (ANXA1) expression, mode of cell death and cell cycle arrest in different human leukemic cell lines.

Methods

Cells viability were examined by MTT assay and ANXA1 quantification via Enzyme-linked Immunosorbent Assay. Cell cycle and apoptosis were examined by flow cytometer and phagocytosis effect was evaluated using haematoxylin-eosin staining.

Results

Coumestrol significantly (p < 0.05) reduced the total level of ANXA1 in both K562 and U937 cells and genistein significantly (p < 0.05) reduced it in K562, Jurkat and U937 cells, meanwhile estradiol and daidzein induced similar reduction in U937 and Jurkat cells. Coumestrol and daidzein induced apoptosis in K562 and Jurkat cells, while genistein and estradiol induced apoptosis in all tested cells. Coumestrol and estradiol induced cell cycle arrest at G2/M phase in K562 and Jurkat cells with an addition of U937 cells for estradiol. Genistein induced cell cycle arrest at S phase for both K562 and Jurkat cells. However, daidzein induced cell cycle arrest at G0/G1 phase in K562, and G2/M phase of Jurkat cells. Coumestrol, genistein and estradiol induced phagocytosis in all tested cells but daidzein induced significant (p < 0.05) phagocytosis in K562 and Jurkat cells only.

Conclusion

The selected phytoestrogens induced cell cycle arrest, apoptosis and phagocytosis and at the same time they reduced ANXA1 level in the tested cells. The IC50 value of phytoestrogens was undetectable at the concentrations tested, their ability to induce leukemic cells death may be related with their ability to reduce the levels of ANXA1. These findings can be used as a new approach in cancer treatment particularly in leukemia.

中文翻译：

植物雌激素在人类白血病细胞系中诱导细胞死亡和调节膜联蛋白 A1

背景

植物雌激素是多酚类植物化合物，其结构类似于内源性哺乳动物雌激素 17β-雌二醇。膜联蛋白 A1 (ANXA1) 是一种内源性蛋白质，可抑制环加氧酶 2 (COX-2) 和磷脂酶 A2、信号转导、DNA 复制、细胞转化和细胞凋亡的介导。

客观的

本研究旨在确定选定的植物雌激素对不同人类白血病细胞系中膜联蛋白 A1 (ANXA1) 表达、细胞死亡模式和细胞周期停滞的影响。

方法

通过MTT测定和通过酶联免疫吸附测定的ANXA1定量检查细胞活力。流式细胞仪检测细胞周期和细胞凋亡，苏木精-伊红染色评价吞噬作用。

结果

香豆雌酚显着（p < 0.05）降低了 K562 和 U937 细胞中 ANXA1 的总水平，染料木黄酮显着降低了 K562、Jurkat 和 U937 细胞中的 ANXA1 总水平（p < 0.05），同时雌二醇和黄豆苷元在 U937 和 Jurkat 细胞中也诱导了类似的降低。香豆素和黄豆苷元在 K562 和 Jurkat 细胞中诱导细胞凋亡，而染料木黄酮和雌二醇在所有测试细胞中诱导细胞凋亡。香豆雌酚和雌二醇在 K562 和 Jurkat 细胞中诱导细胞周期停滞在 G2/M 期，并添加用于雌二醇的 U937 细胞。金雀异黄素诱导 K562 和 Jurkat 细胞的 S 期细胞周期停滞。然而，黄豆苷元在 K562 的 G0/G1 期和 Jurkat 细胞的 G2/M 期诱导细胞周期停滞。香豆雌酚、染料木黄酮和雌二醇在所有测试细胞中诱导吞噬作用，但黄豆苷元诱导显着（p < 0.