The Effect of the Persian Gulf Jellyfish (Cassiopea andromeda) Venom on the Expression of P15, P21, P53, DNMT1, and Bcl-2 in Acute Lymphoblastic Leukemia Jurkat Cells.

Reza Dehghani, Ali Amrooni, Fatemeh Hosseinpour-Soleimani, Gholamhossein Mohebbi, Narges Obeidi
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Abstract

Background: One of the acute hematologic malignancies is acute lymphoblastic leukemia (ALL), which is formed in B or T lymphocyte stem cells. Regarding the increasing tendency to herbal and marine studies and unclear characteristics of Cassiopea andromeda Venom, this study was performed to determine its effects on Jurkat cells as a model for T-ALL. Materials and Methods: In this experimental study, the cells were treated with a variety of concentrations of Cassiopea andromeda venom at different periods and times. Growth inhibition and toxic effects of Cassiopea andromeda Venom were evaluated by methyl thiazole tetrazolium salt reduction (MTT test). The flow cytometry analysis was carried out using 7-aminoactinomycin D (7AAD) and Annexin V stains to evaluate the venom's effect on apoptotic pathways. Besides, Real-Time PCR was performed to evaluate the relative gene expression. Results: Cassiopea andromeda venom inhibited the growth of Jurkat cells in a concentration and time manner. Jurkat cell growth was inhibited by 48.9% after 72 hours of treatment with 250µg/mL Cassiopea andromeda venom. The venom increased the apoptotic process through the upregulation of p15INK4b and P53 proteins and downregulation of Bcl-2, p21 WAF1/CIP1, and DNMT1 in the Jurkat cell line. Conclusion: Considering the growth inhibitory property of Cassiopea andromeda Venom, we recommend it as a part of combinational medication for treating ALL in animal trials and for other leukemias in vitro studies.

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波斯湾水母毒对急性淋巴细胞白血病Jurkat细胞P15、P21、P53、DNMT1和Bcl-2表达的影响。
背景:急性淋巴细胞白血病(ALL)是急性血液系统恶性肿瘤之一,由B或T淋巴细胞干细胞形成。关于草药和海洋研究的增加趋势以及仙后座仙女毒的不清楚特征,本研究旨在确定其对Jurkat细胞的影响,作为T-ALL的模型。材料和方法:在本实验研究中,用不同浓度的仙后座仙女座毒液在不同时期和时间处理细胞。采用甲基噻唑四唑盐还原法(MTT法)评价仙后座毒的生长抑制和毒性作用。使用7-氨基放线菌素D(7AAD)和膜联蛋白V染色进行流式细胞术分析,以评估毒液对细胞凋亡途径的影响。此外,还进行了实时PCR来评估相关基因的表达。结果:仙后座毒对Jurkat细胞的生长有一定的抑制作用,且具有一定的浓度和时间效应。用250µg/mL仙后座仙女座毒液处理72小时后,Jurkat细胞生长受到48.9%的抑制。在Jurkat细胞系中,毒液通过上调p15INK4b和P53蛋白以及下调Bcl-2、p21 WAF1/CIP1和DNMT1来增加细胞凋亡过程。结论:考虑到仙后座仙女毒的生长抑制特性,我们建议在动物试验和其他体外白血病研究中将其作为治疗ALL的联合药物的一部分。
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