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西红花苷通过内源性途径促进人EB病毒转化的B淋巴细胞凋亡。

Crocin Promotes Apoptosis in Human EBV-Transformed B-Lymphocyte via Intrinsic Pathway.

作者信息

Jahromi Abdolreza Sotoodeh, Kargar Mohammad, Kafilzadeh Farshid, Jamalidoust Marzieh, Moradzadeh Maliheh

机构信息

Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran.

Department of Clinical Virology, Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Namazi Hospital, Shiraz, Iran.

出版信息

Mediterr J Hematol Infect Dis. 2021 Jul 1;13(1):e2021049. doi: 10.4084/MJHID.2021.049. eCollection 2021.

Abstract

BACKGROUND

As a major carotenoid in saffron, crocin demonstrates potent anti-cancer impacts. However, its anti-lymphoma effects remain vague, especially in the human EBV-associated B-cell lymphoproliferative disorders. This study examined crocin's apoptogenic potential and its underlying mechanism in CO 88BV59-1 cell line vs. normal human peripheral blood B cells.

METHODS

CO 88BV59-1 cells were treated with crocin alone or in combination with vincristine for up to 72 h. The cell viability was examined using a resazurin assay. Flow cytometry using annexin V and propidium iodide labeling was performed to detect apoptotic cells. Also, the expression levels of genes and proteins involved in apoptosis (CASP3, CASP8, CASP9, P53, Bax, and Bcl-2) were respectively determined via real-time PCR and Western blot analysis.

RESULTS

Crocin concentration-dependently reduced cell viability in CO 88BV59-1 cells with no significant toxicity toward normal B cells. Similar to vincristine, crocin significantly increased apoptosis in these cells during 72 h of incubation. Furthermore, the combination of crocin (80 μM) and vincristine (1 μM) enhanced apoptosis in CO 88BV59-1 cells. Therefore, this synergistic effect was detected in human EBV-transformed B-lymphocyte. CASP3, CASP9, P53, and Bax/Bcl-2 ratio expressions were significantly raised in CO 88BV59-1 cells, whereas CASP8 was unaltered. It was proposed that crocin promoted apoptosis in CO 88BV59-1 cells in a time- and concentration-dependent manner via the induction of the intrinsic pathway.

CONCLUSION

The results suggest that crocin may serve as a good alternative/coadjuvant to vincristine in EBV-associated B-cell lymphoproliferative disorders.

摘要

背景

作为藏红花中的主要类胡萝卜素,西红花苷具有强大的抗癌作用。然而,其抗淋巴瘤作用仍不明确,尤其是在人类EB病毒相关的B细胞淋巴增殖性疾病中。本研究检测了西红花苷在CO 88BV59-1细胞系与正常人外周血B细胞中的促凋亡潜力及其潜在机制。

方法

CO 88BV59-1细胞单独用西红花苷处理或与长春新碱联合处理长达72小时。使用刃天青检测法检测细胞活力。采用膜联蛋白V和碘化丙啶标记的流式细胞术检测凋亡细胞。此外,分别通过实时聚合酶链反应和蛋白质免疫印迹分析确定凋亡相关基因(CASP3、CASP8、CASP9、P53、Bax和Bcl-2)和蛋白的表达水平。

结果

西红花苷浓度依赖性地降低CO 88BV59-1细胞的活力,对正常B细胞无明显毒性。与长春新碱相似,西红花苷在孵育72小时期间显著增加这些细胞的凋亡。此外,西红花苷(80 μM)与长春新碱(1 μM)联合使用可增强CO 88BV59-1细胞的凋亡。因此,在人EB病毒转化的B淋巴细胞中检测到这种协同效应。CO 88BV59-1细胞中CASP3、CASP9、P53和Bax/Bcl-2比值的表达显著升高,而CASP8未改变。据推测,西红花苷通过诱导内源性途径以时间和浓度依赖性方式促进CO 88BV59-1细胞凋亡。

结论

结果表明西红花苷在EB病毒相关的B细胞淋巴增殖性疾病中可能是长春新碱的良好替代/辅助药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b0/8265378/0f547d244644/mjhid-13-1-e2021049f1.jpg

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