Department of Biology, Boston University, Boston, MA 02215, USA.
Cancer Lett. 2012 May 1;318(1):53-60. doi: 10.1016/j.canlet.2011.11.035. Epub 2011 Dec 6.
In this report, we investigated the effects of the natural product parthenolide on human B-lymphoma cell lines. We show that parthenolide inhibited NF-κB transcription factor c-Rel (REL). In addition, the sensitivity of several human B-lymphoma cell lines to parthenolide-induced apoptosis inversely correlated with their levels of anti-apoptosis protein Bcl-X(L). Furthermore, ectopic expression of Bcl-X(L) (but not Bcl-2) in two B-lymphoma cell lines decreased their sensitivity to parthenolide-induced apoptosis. Finally, over-expression of a transforming mutant of REL, which increased expression of endogenous Bcl-X(L), decreased the sensitivity of BJAB B-lymphoma cells to parthenolide-induced apoptosis. These results demonstrate that the NF-κB target gene products Bcl-X(L) and Bcl-2 can play different roles in protecting B-lymphoma cells from chemical-induced apoptosis.
在本报告中,我们研究了天然产物小白菊内酯对人 B 淋巴细胞瘤细胞系的影响。我们发现小白菊内酯抑制 NF-κB 转录因子 c-Rel(REL)。此外,几种人 B 淋巴细胞瘤细胞系对小白菊内酯诱导的细胞凋亡的敏感性与它们的抗凋亡蛋白 Bcl-X(L)水平呈反比。此外,在两种 B 淋巴细胞瘤细胞系中异位表达 Bcl-X(L)(而不是 Bcl-2)可降低它们对小白菊内酯诱导的细胞凋亡的敏感性。最后,表达内源性 Bcl-X(L)增加的 REL 转化突变体的过表达降低了 BJAB B 淋巴细胞瘤细胞对小白菊内酯诱导的细胞凋亡的敏感性。这些结果表明,NF-κB 靶基因产物 Bcl-X(L)和 Bcl-2 可以在保护 B 淋巴细胞瘤细胞免受化学诱导的细胞凋亡方面发挥不同的作用。