Gholami Omid, Jeddi-Tehrani Mahmood, Iranshahi Mehrdad, Zarnani Amir Hassan, Ziai Seyed Ali
Physiology and Pharmacology Department, Faculty of Medicine, Sabzevar University of Medical Sciences.
Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Iran J Pharm Res. 2014 Fall;13(4):1387-92.
Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the western world and exists as subtypes with very different clinical courses. Myeloid cell leukemia 1 (Mcl-1) is one member of Bcl-2 family proteins that has been shown to be expressed in various tissues and malignant cells, including CLL, where its expression is significantly associated with a failure to achieve complete remission following cytotoxic therapy. Induction of apoptosis by prenylated coumarin, umbelliprenin, in Jurkat cells was previously shown. We examined whether umbelliprenin can down-regulate Mcl-1 gene and protein in Jurkat cells. In this regard cells were incubated by umbelliprenin, and then down- regulation of Mcl-1 gene was studied by Real Time PCR method. Moreover, down-regulation of Mcl-1 protein was studied by western blot analysis. We showed that, expression of Mcl-1 mRNA was increased from 1 hour to 3 hours incubation, but this increase has a scale down pattern. Moreover umbelliprenin could inhibit Mcl-1 protein. In conclusion umbelliprenin treatment modulates Mcl-1 expression at both the transcriptional and posttranslational levels.
慢性淋巴细胞白血病（CLL）是西方世界最常见的B细胞恶性肿瘤，存在临床病程差异很大的多种亚型。髓样细胞白血病1（Mcl-1）是Bcl-2家族蛋白的一员，已证实在包括CLL在内的各种组织和恶性细胞中均有表达，其表达与细胞毒性治疗后未能实现完全缓解显著相关。此前已证实异戊烯化香豆素——伞形异戊烯素可诱导Jurkat细胞凋亡。我们研究了伞形异戊烯素是否能下调Jurkat细胞中的Mcl-1基因和蛋白。在这方面，用伞形异戊烯素孵育细胞，然后通过实时聚合酶链反应法研究Mcl-1基因的下调情况。此外，通过蛋白质印迹分析研究Mcl-1蛋白的下调情况。我们发现，孵育1小时到3小时期间，Mcl-1 mRNA的表达增加，但这种增加呈下降趋势。此外，伞形异戊烯素可抑制Mcl-1蛋白。总之，伞形异戊烯素处理可在转录和翻译后水平调节Mcl-1的表达。
