Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
Physiology and Biophysics Program, ICBM, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
Toxins (Basel). 2020 Mar 13;12(3):179. doi: 10.3390/toxins12030179.
Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2). These toxins are potent protein Ser/Thr phosphatase inhibitors, mainly type 1 protein phosphatase (PP1) and type 2A protein phosphatase (PP2A). Different effects have been reported at the cellular, molecular and genetic levels. In this study, changes in cell survival and cell mobility induced by OA, DTX-1 and DTX-2 were determined in epithelial cell lines of the colon and colon cancer. The cell viability results showed that tumoral cell lines were more resistant to toxins than the nontumoral cell line. The results of the functional assays for testing cell migration, evaluation of cell death and the expression of proteins associated with cell adhesion showed a dual effect of toxins since in the nontumoral cell line, a greater induction of cell death, presumably by anoikis, was detected. In the tumoral cell lines, there was an induction of a more aggressive phenotype characterized by increased resistance to toxins, increased migration and increased FAK activation. In tumoral cell lines of colon cancer, OA, DTX-1/DTX-2 induce a more aggressive phenotype.
腹泻性贝类毒素（DSP）是一种由摄入受脂溶性和热稳定毒素污染的贝类引起的综合征，这些毒素包括冈田酸（OA）、石房蛤毒素-1（DTX-1）和石房蛤毒素-2（DTX-2）。这些毒素是有效的蛋白丝氨酸/苏氨酸磷酸酶抑制剂，主要是 1 型蛋白磷酸酶（PP1）和 2A 型蛋白磷酸酶（PP2A）。在细胞、分子和遗传水平上已经报道了不同的作用。在这项研究中，在结肠和结肠癌的上皮细胞系中，测定了 OA、DTX-1 和 DTX-2 诱导的细胞存活和细胞迁移变化。细胞活力结果表明，肿瘤细胞系比非肿瘤细胞系对毒素更具抗性。用于测试细胞迁移、评估细胞死亡和与细胞黏附相关的蛋白表达的功能测定结果表明，毒素具有双重作用，因为在非肿瘤细胞系中，检测到更多的细胞死亡诱导，推测是通过失巢凋亡。在肿瘤细胞系中，存在诱导更具侵袭性的表型的作用，其特征是对毒素的抗性增加、迁移增加和 FAK 激活增加。在结肠癌的肿瘤细胞系中，OA、DTX-1/DTX-2 诱导更具侵袭性的表型。
