Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Anticancer Res. 2010 Apr;30(4):1209-15.
Cytolysins are pore-forming toxins that show anticancer activity by a mechanism hitherto poorly investigated.
To investigate how cytolysins are cytotoxic to resistant cancer cells, proliferation and cell death were evaluated on U87 glioblastoma cells treated with toxin Bc2 or equinatoxin-II (EqTx-II).
Toxins Bc2 and EqTx-II decreased cell viability and increased lactate dehydrogenase (LDH) release in a concentration-dependent manner. Swollen, dead or dying cells were negative for TUNEL staining. The pre-treatment with inhibitors of mitogen-activated/extracellular regulated kinase (MEK1), protein kinase C (PKC) or Ca(2+)/calmodulin-dependent kinase II (CaMKII) blocked the toxic effects of toxin Bc2 and EqTx-II, suggesting that calcium entry, activation of MEK1, PKC and CaMKII pathways are involved in the cytotoxicity induced by these cytolysins.
Cytolysins were shown to be toxic to glioblastoma cells by activating several intracellular signaling pathways and resulting in necrosis-like cell death.
细胞溶解素是一种形成孔的毒素，其抗癌活性的机制迄今研究甚少。
为了研究细胞溶解素如何对耐药癌细胞产生细胞毒性，我们用毒素 Bc2 或海葵毒素-II（EqTx-II）处理 U87 神经胶质瘤细胞，评估细胞增殖和细胞死亡情况。
毒素 Bc2 和 EqTx-II 呈浓度依赖性降低细胞活力并增加乳酸脱氢酶（LDH）释放。肿胀、死亡或濒死细胞的 TUNEL 染色呈阴性。用丝裂原激活/细胞外调节激酶（MEK1）、蛋白激酶 C（PKC）或钙/钙调蛋白依赖性激酶 II（CaMKII）抑制剂预处理可阻断毒素 Bc2 和 EqTx-II 的毒性作用，表明钙内流、MEK1、PKC 和 CaMKII 途径的激活参与了这些细胞溶解素诱导的细胞毒性。
细胞溶解素通过激活多种细胞内信号通路并导致类似坏死的细胞死亡，对神经胶质瘤细胞具有毒性。
