Coskun Deniz, Obakan Pinar, Arisan Elif Damla, Çoker-Gürkan Ajda, Palavan-Ünsal Narçin
Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
Exp Cell Res. 2015 Oct 15;338(1):10-21. doi: 10.1016/j.yexcr.2015.08.015. Epub 2015 Aug 28.
Epibrassinolide (EBR), a steroid-derived plant growth regulator, has been recently suggested as an apoptotic inducer in different cancer cells. In this experimental study, we investigated the potential apoptotic effect of EBR on stress-related and survival signaling molecules in colon carcinoma cells. EBR decreased cell viability and colony formation in HCT 116 and HT-29 colon carcinoma cells. The inactivation of PI3K/AKT by EBR treatment led to upregulation of Foxo3a, which in turn induced apoptosis in HCT 116 and HT-29 cells. In addition, the upstream non-receptor protein tyrosine kinase Src was found elevated allowing to the upregulation of p38, stress-activated protein kinase/Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2 and their target genes c-jun, c-fos and c-myc in a time-dependent manner in HCT 116 cells within 48h. The alterations in PA metabolism caused intracellular PA pool decrease. The upregulation of pro-apoptotic Bak, Bax, Puma and Bim were accompanied with the decrease in Mcl-1 in HCT 116 and Bcl-xL expression profiles in HT-29 following 48h EBR treatment. We suggest that the upregulation of Bim expression levels might be related with one of the PI3K/AKT target transcription factor Foxo3a, which was dephosphorylated by EBR treatment in HCT 116 and HT-29 cells.
表油菜素内酯（EBR）是一种类固醇衍生的植物生长调节剂，最近被认为是不同癌细胞中的凋亡诱导剂。在本实验研究中，我们研究了EBR对结肠癌细胞中应激相关和存活信号分子的潜在凋亡作用。EBR降低了HCT 116和HT-29结肠癌细胞的细胞活力和集落形成。EBR处理使PI3K/AKT失活，导致Foxo3a上调，进而诱导HCT 116和HT-29细胞凋亡。此外，发现在48小时内，上游非受体蛋白酪氨酸激酶Src在HCT 116细胞中升高，从而使p38、应激激活蛋白激酶/ Jun氨基末端激酶和细胞外信号调节激酶1/2及其靶基因c-jun、c-fos和c-myc呈时间依赖性上调。PA代谢的改变导致细胞内PA池减少。48小时EBR处理后，HCT 116细胞中促凋亡蛋白Bak、Bax、Puma和Bim的上调伴随着Mcl-1的减少以及HT-29细胞中Bcl-xL表达谱的改变。我们认为Bim表达水平的上调可能与PI3K/AKT靶转录因子Foxo3a之一有关，在HCT 116和HT-29细胞中，EBR处理使Foxo3a去磷酸化。
