2012 ©
Journal Publication
Title of Article Anthocyanin complex exerts anti-cholangiocarcinoma activities and improves the efficacy of drug treatment in a gemcitabine-resistant cell line 
Date of Acceptance 1 March 2018 
     Title of Journal International Journal of Oncology 
     Standard ISI 
     Institute of Journal Spandidos Publications 
     ISBN/ISSN 1019-6439 
     Volume 2018 
     Year of Publication 2018 
     Abstract Cholangiocarcinoma (CCA) is a deleterious bile duct tumor with poor prognosis and is relatively resistant to chemotherapy. Therefore, alternative or supplementary agents with anticancer and chemosensitizing activities may be useful for the treatment of CCA. A novel anthocyanin complex (AC) nanoparticle, developed from extracts of cobs of purple waxy corn and petals of blue butterfly pea, has exhibited chemopreventive potential in vivo. In the present study, the anti-CCA activities of AC and their underlying molecular mechanisms were investigated further in vitro using a CCA cell line (KKU213). The potential use of AC as a chemosensitizer was also evaluated in a gemcitabine-resistant CCA cell line (KKU214GemR). It was demonstrated that AC treatment suppressed proliferation of KKU213 CCA cells in dose- and time-dependent manners. AC treatment also induced apoptosis and mitochondrial superoxide production, decreased clonogenicity of CCA cells, and downregulated forkhead box protein M1 (FOXM1), nuclear factor-κB (NF-κB) and pro-survival protein B-cell lymphoma-2 (Bcl-2). The expression of endoplasmic reticulum (ER) stress-response proteins, including protein kinase RNA-like ER kinase, phosphorylated eIF2α, eukaryotic initiation factor 2α and activating transcription factor 4, also decreased following AC treatment. It was also identified that AC treatment inhibited KKU214GemR cell proliferation in dose- and time-dependent manners. Co-treatment of KKU214GemR cells with low doses of AC together with gemcitabine significantly enhanced efficacy of the latter against this cell line. Therefore, it is suggested that AC treatment is cytotoxic to KKU213 cells, possibly via downregulation of FOXM1, NF-κB, Bcl-2 and the ER stress response, and by induction of mitochondrial superoxide production. AC also sensitizes KKU214GemR to gemcitabine treatment, which may have potential for overcoming drug resistance of CCA. 
     Keyword Anthocyanin complex, Chemosensitizer, Cholangiocarcinoma, Forkhead Box Protein M1, Endoplasmic reticulum stress, Gemcitabine 
547100011-6 Mr. KITTI INTUYOD [Main Author]
Graduate School Doctoral Degree

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Level of Publication นานาชาติ 
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