Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
Int J Oncol. 2013 Dec;43(6):1799-808. doi: 10.3892/ijo.2013.2128. Epub 2013 Oct 4.
Sialic-acid binding lectin (SBL) isolated from bullfrog (Rana catesbeiana) oocytes is a multifunctional protein which has lectin activity, ribonuclease activity and cancer-selective antitumor activity. It has been reported that SBL induces apoptosis accompanied by rigid mitochondrial perturbation, which indicates mediation of the intrinsic pathway. However, the mechanism of the antitumor effect of SBL has not been fully elucidated. We report, here, that ER stress is evoked in SBL-treated cells. We show that caspase-4, an initiator caspase of ER stress-mediated apoptosis was activated, and inhibition of caspase-4 resulted in significant attenuation of apoptosis induced by SBL. We analyzed the precise mechanism of activation of the caspase cascade induced by SBL, and found that caspase-9 and -4 are activated upstream of activation of caspase-8. Further study revealed that SBL induces the mitochondrial and ER stress-mediated pathways independently. It is noteworthy that SBL can induce cancer-selective apoptosis by multiple apoptotic signaling pathways, and it can serve as a candidate molecule for anticancer drugs in a novel field.
从牛蛙（Rana catesbeiana）卵母细胞中分离得到的唾液酸结合凝集素（SBL）是一种多功能蛋白，具有凝集素活性、核糖核酸酶活性和肿瘤选择性抗肿瘤活性。据报道，SBL 诱导伴随刚性线粒体扰动的细胞凋亡，这表明其介导了内在途径。然而，SBL 的抗肿瘤作用机制尚未完全阐明。我们在这里报告 SBL 处理的细胞中会引发内质网应激。我们表明，内质网应激介导凋亡的起始半胱天冬酶 caspase-4 被激活，并且 caspase-4 的抑制导致 SBL 诱导的细胞凋亡显著减弱。我们分析了 SBL 诱导的胱冬酶级联反应的精确机制，发现 caspase-9 和 caspase-4 在 caspase-8 的激活之前被激活。进一步的研究表明，SBL 可独立诱导线粒体和内质网应激介导的途径。值得注意的是，SBL 可以通过多种凋亡信号通路诱导肿瘤选择性凋亡，它可以作为一个新领域抗癌药物的候选分子。
