書誌事項
- タイトル別名
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- Search for chromone derivatives that show high tumor-specificity against human oral squamous cell carcinoma, and evaluation of their adverse effects on normal cells
説明
<p>Introduction: Many anticancer drugs have been reported to cause serious side effects such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that among 291 chromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines, exceeding that of doxorubicin and 5-FU. In this study, newly synthesized 65 chromone derivatives were investigated for their TS and side effects. Method: The 50% cytotoxic concentration (CC50) for four OSCC (Ca9-22, HSC-2, HSC-3, HSC-4), normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell), oral epithelial cells (HOK, HGEP) and differentiated PC12 neuronal cells was determined from the dose-response curve. TS was calculated as the ratio of the mean CC50 for normal cells to that for OSCC. Apoptosis was assayed by cell cycle analysis. Results and Discussion: Newly synthesized indolychromones,indole-aurone hybrids,capsaicin derivatives,6,7-styrylchromones,3-benzylidenechromanones showed much lower TS value than compound A. Compound A should much lower keratinocyte toxicity than doxorubicin and 5-FU. 20 h treatment of Ca9-22 with compound A induced plateau level of cytotoxicity and accumulation of subG1 and G2/M population. In silico study suggests the inhibition of compound A against the estrogen related receptor-alpha signaling pathway, that is identified as an adverse marker for breast cancer progression and poor prognosis.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 96 (0), 1-B-P-079-, 2022
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390294562485517056
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可