Caffeine Has a Synergistic Anticancer Effect with Cisplatin via Inhibiting Fanconi Anemia Group D2 Protein Monoubiquitination in Hepatocellular Carcinoma Cells
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- Oda Yuichiro
- The Third Department of Clinical Pharmacy, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
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- Hidaka Muneaki
- The Third Department of Clinical Pharmacy, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
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- Suzuki Akito
- The Third Department of Clinical Pharmacy, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
書誌事項
- タイトル別名
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- Caffeine Has a Synergistic Anticancer Effect with Cisplatin <i>via</i> Inhibiting Fanconi Anemia Group D2 Protein Monoubiquitination in Hepatocellular Carcinoma Cells
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<p>Cisplatin is an anticancer agent and induces DNA interstrand cross-links (ICLs). ICLs activate various signaling processes and induce DNA repair pathways, including the Fanconi anemia (FA) pathway. FA complementation group D2 (FANCD2) is monoubiquitinated in response to DNA damage, leading to activation of the DNA double-strand-break repair protein, RAD51. Caffeine increases the anticancer activity of cisplatin by inhibiting DNA repair; however, details of the mechanism remain unclear. We investigated the mechanism responsible for the synergistic anticancer effect of cisplatin and caffeine in HepG2 human hepatocellular carcinoma cells, focusing on the FA pathway. Caffeine (≥100 µg/mL) significantly enhanced the antiproliferative activity induced by 3.8 µg/mL cisplatin. Caffeine (200 µg/mL) promoted apoptosis and inhibited the increase in the proportion of viable cells in S phase that occurred in the presence of 3.8 µg/mL cisplatin. Both FANCD2 monoubiquitination and RAD51 expression were significantly inhibited by co-treatment with 200 µg/mL caffeine and 3.8 µg/mL cisplatin compared with cisplatin alone. In conclusion, caffeine enhances the anticancer effect of cisplatin by inhibiting FANCD2 monoubiquitination. In HepG2 cells, caffeine might inhibit the FA pathway and thereby regulate DNA damage responses such as DNA repair and apoptosis.</p>
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 40 (11), 2005-2009, 2017
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679608308352
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- NII論文ID
- 130006191807
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 028602440
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- PubMed
- 28855448
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可