The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron’s anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.

中文翻译：

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藏红花粗品和化合物限制了MACC1依赖的细胞增殖和结直肠癌细胞的迁移。

大肠癌（CRC）患者的高死亡率与转移性传播直接相关。但是，专门用于转移的治疗选择仍然有限。我们先前确定与结肠癌1（MACC1）相关的转移是主要的因果转移诱导基因。许多研究证实了其作为转移风险的生物标志物的价值。我们研究了藏红花对MACC1诱导的癌细胞生长和运动性的抑制作用。藏红花原油以浓度和MACC1依赖性方式限制了表达MACC1的CRC细胞的增殖和迁移。藏红花会延迟G2 / M期的细胞周期进程，并且不会诱导细胞凋亡。救援实验表明，这些作用是可逆的。对活性藏红花化合物的分析表明，番红花是再现总藏红花原油效果的主要化合物。我们显示了MACC1与癌症干细胞（CSC）标记DCLK1的相互作用，这有助于在不同肿瘤实体中形成转移。番红花提取物还原了DCLK1，其中番红花可导致还原。藏红花在表达MACC1的细胞中的抗增殖和抗迁移作用是由番红花素通过DCLK1下调介导的。这项研究是首次鉴定出基于番红花的化合物，通过新型靶标MACC1来限制癌细胞的增殖和活力发展。番红花提取物还原了DCLK1，其中番红花可导致还原。藏红花在表达MACC1的细胞中的抗增殖和抗迁移作用是由番红花素通过DCLK1下调介导的。这项研究是首次鉴定出基于番红花的化合物，通过新型靶标MACC1来限制癌细胞的增殖和活力发展。番红花提取物还原了DCLK1，其中番红花可导致还原。藏红花在表达MACC1的细胞中具有抗增殖和抗迁移的作用，是通过DCLK1下调而由番红花介导的。这项研究是首次鉴定出基于番红花的化合物，通过新型靶标MACC1来限制癌细胞的增殖和活力发展。