Epibrassinolide alters PI3K/MAPK signaling axis via activating Foxo3a-induced mitochondria-mediated apoptosis in colon cancer cells

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• 作者：Deniz Coskun¹ ; Pinar Obakan¹ ; Elif Damla Arisan ; ^{d.arisan@iku.edu.tr" class="auth_mail" title="E-mail the corresponding author} ; Ajda &Ccedil ; oker-Gü ; rkan ; Nar&ccedil ; in Palavan-Ü ; nsal
• 关键词：AR ; Androgen receptor ; AZ ; Antizyme ; AZI ; Antizyme inhibitor ; AP-1 ; Activator protein 1 ; BR ; Brassinosteroid ; Bcl-2 ; B-cell lymphoma 2 ; DiOC6 ; 3 ; 3&prime ; -dihexyloxacarbocyanineiodide ; CHENSpm ; N1-ethyl-N11-((cycloheptyl)methy)-4 ; 8-diazaundecane ; DAPI ; 4&prime ; 6-diamidino-2-phenylindole ; DMSO ; Dimethyl sulfoxide ; EBR ; Epibrassinolide ; EDTA ; Ethylenediaminetetraaceticacid ; ERK1/2 ; extracellular signal-regulated kinase 1/2 ; Foxo ; Forkhead/Winged Helix Box Class O ; HPLC ; High pressure liquid chroma
• 刊名：Experimental Cell Research
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：338
• 期：1
• 页码：10-21
• 全文大小：2523 K

文摘

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 48 h. 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-x_L expression profiles in HT-29 following 48 h 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.