title: Epibrassinolide alters PI3K/MAPK signaling axis via activating Foxo3a-induced mitochondria-mediated apoptosis in colon cancer cells.
abstract: 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.
authors: Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
authors: Deniz
authors: D
authors: Coskun
authors: Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
authors: Pinar
authors: P
authors: Obakan
authors: Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey. Electronic address: d.arisan@iku.edu.tr.
authors: Elif Damla
authors: ED
authors: Arisan
authors: Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
authors: Ajda
authors: A
authors: Çoker-Gürkan
authors: Istanbul Kultur University, Department of Molecular Biology and Genetics, Ataköy Campus, 34156 Bakirkoy, Istanbul, Turkey.
authors: Narçin
authors: N
authors: Palavan-Ünsal
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D060406:Brassinosteroids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D060406:Brassinosteroids; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D011073:Polyamines; D013260:Steroids, Heterocyclic; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C023623:brassinolide
keywords: AKT; Apoptosis; Colon cancer; Epibrassinolide; Foxo3a; PI3K; Polyamines