Camalexin, an indole phytoalexin, inhibits cell proliferation, migration, and mammosphere formation in breast cancer cells via the aryl hydrocarbon receptor
Camalexin, an indole phytoalexin, inhibits cell proliferation, migration, and mammosphere formation in breast cancer cells via the aryl hydrocarbon receptor
复制标题
DOI：
10.1007/s11418-021-01560-8
复制
发表时间：
2021-08
影响因子：
3.3
通讯作者：
Naoya Yamashita;C. Taga;Moeno Ozawa;Yuichiro Kanno;Noriko Sanada;R. Kizu
中科院分区：
文献类型：
--
作者：
Naoya Yamashita;C. Taga;Moeno Ozawa;Yuichiro Kanno;Noriko Sanada;R. Kizu
乳腺癌是全世界妇女中最常见的癌症。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是拟南芥等十字花科植物中主要的吲哚类植物抗毒素。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。我们以前报道，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用作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抑制AhR表达乳腺癌细胞中乳腺球形成的作用大于缺乏AhR表达的乳腺癌细胞。总之，数据表明，camalexin是一种新的AhR激动剂，并且camalexin对细胞增殖、迁移和乳腺球形成的抑制涉及AhR的激活。我们的研究结果表明，camalexin，AhR激动剂，可能是一种新的乳腺癌治疗药物。
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 inArabidopsis thalianaand 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.