title: N6-Isopentenyladenosine promoted HeLa cell apoptosis through inhibitions of AKT and transforming growth factor β-activated kinase 1 activation.
abstract: N6-Isopentenyladenosine, a member of the family of plant hormones, possesses anti-cancer activities on a number of cancer cell lines. However, its mode of action in cervical cancer cell remains poorly understood. Our computational docking studies showed that N6-Isopentenyladenosine could bind with the really interesting new gene domain of tumor necrosis factor receptor-associated factor 6, which is an ubiquitination E3 ligase. Tumor necrosis factor receptor-associated factor 6-mediated ubiquitination is known to activate both protein kinase B (also known as AKT) and transforming growth factor β-activated kinase 1, and the really interesting new gene domain comprises the core of the ubiquitin ligase catalytic domain. First, we evaluated the effects of iPA on cervical cancer cell line HeLa using MTT and flow cytometry. Second, we examined the effects of iPA on activation of tumor necrosis factor receptor-associated factor 6-mediated downstream targets using western blot or immunoprecipitation. iPA could reduce HeLa cell proliferation through apoptosis, and such anti-cancer activity is associated with inhibitions of both AKT and transforming growth factor β-activated kinase 1 signaling pathways. In addition, suppression of the anti-apoptotic protein Bcl-2 and elevation of the pro-apoptotic protein Bax were also observed. Anti-proliferation properties of iPA are likely due to its binding at the really interesting new gene domain of tumor necrosis factor receptor-associated factor 6 and loss of AKT and transforming growth factor β-activated kinase 1 activities as a result of functional modulations of tumor necrosis factor receptor-associated factor 6. These results support the emerging notion that tumor necrosis factor receptor-associated factor 6 could serve as a viable target for developing new cancer therapeutics.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007541:Isopentenyladenosine / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D062105:Molecular Docking Simulation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D054875:Ubiquitination; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D007541:Isopentenyladenosine; D020930:MAP Kinase Kinase Kinases; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D048029:TNF Receptor-Associated Factor 6; D051028:bcl-2-Associated X Protein; D000099151:MAP Kinase Kinase Kinase 7; C494826:BAX protein, human; C000604754:Tifab protein, human
keywords: AKT; HeLa; N6-Isopentenyladenosine; transforming growth factor β–activated kinase 1; tumor necrosis factor receptor–associated factor 6