Abstract Naphthoquinones are naturally occurring metabolites with recognized anti-cancer potential but limited clinical application. This study investigated the molecular mechanism of 8-hydroxy-2-(2-thenoyl)naphtho[2,3-b]thiophene-4,9-dione (1), a new candidate for colorectal cancer (CRC) treatment, using different experimental settings: MTT, clonogenic, wound healing, and cell cycle assays; as well as RNA sequencing. Naphthoquinone 1 selectively reduced the viability and migration of HT-29 cells by G2/M arrest and changes in their transcriptome signature with significant effect on cellular survival, proliferation, angiogenesis, response to interferon, oxidative stress, and immune response. Impact analysis identified ferroptosis and MAPK pathways as significantly affected. In summary, our results suggest that 1 induces the selective death of CRC cells by inducing oxidative stress, ferroptosis, and MAPK inhibition. Graphical abstract

中文翻译：

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一种有前景的萘醌[8-羟基-2-(2-噻吩基羰基)萘并[2,3-b]噻吩-4,9-二酮]通过铁死亡和基于RNA测序的MAPK信号通路抑制发挥抗结直肠癌活性

摘要 萘醌是天然存在的代谢物，具有公认的抗癌潜力，但临床应用有限。本研究调查了 8-hydroxy-2-(2-thenoyl)naphtho[2,3-b] thiophene-4,9-dione (1)（一种治疗结直肠癌 (CRC) 的新候选药物）的分子机制，使用不同的实验设置：MTT、克隆、伤口愈合和细胞周期测定；以及RNA测序。Naphthoquinone 1 通过 G2/M 停滞和转录组特征的变化选择性地降低 HT-29 细胞的活力和迁移，对细胞存活、增殖、血管生成、对干扰素的反应、氧化应激和免疫反应有显着影响。影响分析确定铁死亡和 MAPK 通路受到显着影响。总之，我们的结果表明 1 通过诱导氧化应激、铁死亡和 MAPK 抑制来诱导 CRC 细胞的选择性死亡。图形概要