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最終更新日：2025/02/18
品川 明穂
シナガワ アキホ
(Akiho Shinagawa)
論文
- タイトル
- タイトル（英）
- Resveratrol can differentiate human melanoma stem-like cells from spheroids treated sith all-trans retinoic acid
- 参照URL
- https://researchmap.jp/a.shinagawa/published_papers/49176511
- 著者
- 著者（英）
- Mina Kanai,Akiho Shinagawa,Masako Ota,Nantiga Virgona,Tomohiro Yano
- 担当区分
- 概要
- 概要（英）
- BACKGROUND/AIM: Stem-like cancer cells are believed to be the leading cause of therapy resistance in malignant melanoma (MM). All-trans retinoic acid (ATRA) differentiation therapy is considered a promising approach to eradicate stem-like cancer cells, but some melanoma cells are resistant to ATRA. This study aimed to examine whether resveratrol (RS), a natural polyphenol compound, could improve the response of MM stem-like cells to ATRA and explore the possible underlying mechanisms. MATERIALS AND METHODS: MM stem-like cells were established from a spheroid model of A375 human MM cell line. The response to RES alone and in combination with ATRA, was examined through analysis of cancer stemness, cell viability, and protein expression. RESULTS: The stem-like cells showed resistance to the anticancer drug docetaxel; however, the combination of RES and ATRA augmented the effects of docetaxel. Accordingly, these combinatorial effects were associated with significant inhibition of the expression levels of stemness markers CD133, OCT4, CD271, and ABCG2. The tested combinations also led to a significant increase in melanocyte differentiation marker SOX9, while efficiently suppressing the dedifferentiation marker SOX10. Notably, RES alone effectively up-regulated retinoic acid receptor beta (RARβ) expression and down-regulated crucial mediators like DNMT1, polycomb-group proteins EZH2, and BMI-1, which mechanistically explain how RES enhanced the differentiation-inducing effects of ATRA. CONCLUSION: The resistance of MM stem-like cells to ATRA can be attenuated by RES and combined applications of ATRA and RES provide a promising strategy for MM treatment.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Anticancer research
- 巻
- 44
- 号
- 12
- 開始ページ
- 5283
- 終了ページ
- 5292
- 出版年月
- 2024年12月
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.21873/anticanres.17356
- 共同研究・競争的資金等の研究課題