Therapeutic Potential of RTA 404 in Human Brain Malignant Glioma Cell Lines via Cell Cycle Arrest via p21/AKT Signaling.
Background. Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an...
| Published in: | BioMed Research International pp. 1 - 16 |
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| Main Authors: | , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
3/9/2021
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149334818&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149334818 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 3/9/2021 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 149334818 149334818 149334818 10.1155/2021/5552226 149334818 ppf: 1 ppct: 15 formats: fmt: @attributes: type: P tig: atl: Therapeutic Potential of RTA 404 in Human Brain Malignant Glioma Cell Lines via Cell Cycle Arrest via p21/AKT Signaling. aug: au: Tsai, Tai-Hsin Lieu, Ann-Shung Wang, Yi-Wen Yang, Sheau-Fang Hsu, Yi-Chiang Lin, Chih-Lung affil: Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan sug: subj: Glioma Drug Therapy Hydrocarbons Pharmacodynamics Antineoplastic Agents Pharmacodynamics Cell Line, Tumor Drug Effects Cell Cycle Drug Effects Phosphotransferases Drug Effects Signal Transduction Drug Effects Human In Vitro Studies Apoptosis Drug Effects Cell Movement Drug Effects Flow Cytometry Blotting, Western Cell Proliferation Drug Effects Gene Expression Drug Effects Glycoproteins Drug Effects Treatment Outcomes ab: Background. Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an Nrf2 activator used to inhibit proliferation and induce differentiation and apoptosis in various cancer cells. One new trifluoroethylamide derivative of CDDO, RTA 404, has been found to have increased ability to cross the blood-brain barrier. However, it is not clear what effect it may have on tumorigenesis in GBM. Methods. This in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM840 and U87 MG cell lines with RTA 404 and assessed apoptosis, cell cycle, cell locomotion, and senescence. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. Results. RTA 404 significantly inhibited the proliferation of tumor cells at concentrations higher than 100 nM (p < 0.05) and reduced their locomotion ability. In addition, treatment with RTA 404 led to an accumulation of RTA 404-treated G 2 / M phase cells and apoptosis. An analysis of the p21/AKT expression suggested that RTA 404 may not only help prevent brain cancer but it may also exert antitumor activities in established GBM cells. Conclusion. RTA404 can inhibit proliferation, cell locomotion, cell cycle progression, and induce apoptosis in GBM cells in vitro, possibly through its inhibition of N-cadherin and E-cadherin expression via its inhibition of the AKT pathway. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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