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Cisplatin Relocalizes RNA Binding Protein HuR and Enhances the Oncolytic Activity of E4orf6 Deleted Adenovirus

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Title: Cisplatin Relocalizes RNA Binding Protein HuR and Enhances the Oncolytic Activity of E4orf6 Deleted Adenovirus
Authors: Habiba, Umma Browse this author →KAKEN DB
Hossain, Elora Browse this author
Yanagawa-Matsuda, Aya Browse this author →KAKEN DB
Chowdhury, Abu Faem Mohammad Almas Browse this author →KAKEN DB
Tsuda, Masumi Browse this author →KAKEN DB
Zaman, Asad-uz- Browse this author
Tanaka, Shinya Browse this author →KAKEN DB
Higashino, Fumihiro Browse this author →KAKEN DB
Keywords: ARE
AU-rich element
human antigen R
3 '-UTR
3 '-untranslated region
Cis-diamminedichloroplatinum (CDDP)
Issue Date: Apr-2020
Publisher: MDPI
Journal Title: Cancers
Volume: 12
Issue: 4
Start Page: 809
Publisher DOI: 10.3390/cancers12040809
Abstract: The combination of adenoviruses and chemotherapy agents is a novel approach for human cancer therapeutics. A meticulous analysis between adenovirus and chemotherapeutic agents can help to design an effective anticancer therapy. Human antigen R (HuR) is an RNA binding protein that binds to the AU-rich element (ARE) of specific mRNA and is involved in the export and stabilization of ARE-mRNA. Our recent report unveiled that the E4orf6 gene deleted oncolytic adenovirus (dl355) replicated for certain types of cancers where ARE-mRNA is stabilized. This study aimed to investigate whether a combined treatment of dl355 and Cis-diamminedichloroplatinum (CDDP) can have a synergistic cell-killing effect on cancer cells. We confirmed the effect of CDDP in nucleocytoplasmic HuR shuttling. In vitro and in vivo experiments showed the enhancement of cancer cell death by apoptosis induction and a significant reduction in tumor growth following combination treatment. These results suggested that combination therapy exerted a synergistic antitumor activity by upregulation of CDDP induced cytoplasmic HuR, which led to ARE mRNA stabilization and increased virus proliferation. Besides, the enhanced cell-killing effect was due to the activation of the intrinsic apoptotic pathway. Therefore, the combined treatment of CDDP and dl355 could represent a rational approach for cancer therapy.
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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