Breast cancer is the most commonly diagnosed cancer among women worldwide. Despite a variety of drugs available for the treatment of patients with breast cancer, drug resistance remains a significant clinical problem. Therefore, there is an urgent need to develop drugs with new mechanisms of action. Camalexin is the main indole phytoalexin in Arabidopsis thaliana and other crucifers. Camalexin inhibits the proliferation of various cancer cells. However, the mechanism by which camalexin inhibits cell proliferation remains unclear. In this study, we found that camalexin inhibited cell proliferation and migration of breast cancer cell lines. Furthermore, camalexin also suppressed breast cancer stem cell-derived mammosphere formation. We previously reported that the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) agonist suppresses mammosphere formation. Several compounds with indole structures are known to act as AhR agonists. Therefore, we hypothesized that the inhibition of mammosphere formation by camalexin may involve AhR activation. We found that camalexin increased the nuclear translocation of AhR, AhR-mediated transcriptional activation, and expression of AhR target genes. In addition, camalexin suppressed mammosphere formation in AhR-expressing breast cancer cells more than in the breast cancer cells that lacked AhR expression. Taken together, the data demonstrate that camalexin is a novel AhR agonist and that the inhibition of cell proliferation, migration, and mammosphere formation by camalexin involves the activation of AhR. Our findings suggest that camalexin, an AhR agonist, may be a novel therapeutic agent for breast cancer.

中文翻译：

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Camalexin 是一种吲哚植物抗毒素，通过芳烃受体抑制乳腺癌细胞中的细胞增殖、迁移和乳腺球形成。

乳腺癌是全世界女性中最常被诊断出的癌症。尽管有多种药物可用于治疗乳腺癌患者，但耐药性仍然是一个重要的临床问题。因此，迫切需要开发具有新作用机制的药物。Camalexin 是拟南芥和其他十字花科植物中主要的吲哚植物抗毒素。Camalexin 抑制各种癌细胞的增殖。然而，camalexin 抑制细胞增殖的机制仍不清楚。在这项研究中，我们发现camalexin 抑制乳腺癌细胞系的细胞增殖和迁移。此外，camalexin 还抑制乳腺癌干细胞衍生的乳腺球形成。我们之前报道了配体激活的转录因子芳烃受体 (AhR) 激动剂抑制乳腺球的形成。已知几种具有吲哚结构的化合物可作为 AhR 激动剂。因此，我们假设camalexin对乳腺球形成的抑制可能涉及AhR的激活。我们发现camalexin 增加了AhR 的核转位、AhR 介导的转录激活和AhR 靶基因的表达。此外，camalexin 在表达 AhR 的乳腺癌细胞中比在缺乏 AhR 表达的乳腺癌细胞中更能抑制乳腺球的形成。总之，数据表明camalexin 是一种新型AhR 激动剂，camalexin 对细胞增殖、迁移和乳腺球形成的抑制涉及AhR 的激活。