de Oliveira Figueirôa Evellyne, Aranda-Souza Mary Ângela, Varejão Nathalia, Rossato Franco Aparecido, Costa Rute Alves Pereira, Figueira Tiago Rezende, da Silva Luís Cláudio Nascimento, Castilho Roger Frigério, Vercesi Aníbal Eugênio, Dos Santos Correia Maria Tereza
Laboratório de Glicoproteínas, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife (PE), CEP 50670-420, Brazil.
Instituto de Bioquímica Médica, Programa de Biologia Estrutural, Centro Nacional de Ressonância Magnética Nuclear de Macromoléculas, Universidade Federal do Rio de Janeiro, Rio de Janeiro (RJ) CEP 21941-590, Brazil.
Toxicol In Vitro. 2017 Sep;43:40-46. doi: 10.1016/j.tiv.2017.05.016. Epub 2017 May 25.
Lectins from Cratylia mollis seed have shown potential in vivo antitumor actions, however the mechanism have not yet been addressed. Here we evaluated the antitumor effects of native (pCramoll) and recombinant (rCramoll) lectins from C. mollis against human prostate adenocarcinoma (PC-3) cells. The viability of PC-3 cells was analyzed with the MTT assay and ANNEXIN V/propidium iodide staining. The actions of pCramoll or rCramoll on mitochondrial superoxide production, free cytosolic calcium concentration and mitochondrial membrane potential were evaluated using fluorescent probes (MitoSox Red, Fura 2-AM and safranin O, respectively). pCramoll and rCramoll reduced the viability of PC-3 cells in a dose-dependent manner. Both lectins increased the generation of mitochondrial superoxide as well as the concentration of cytosolic calcium. These changes led to a decrease in oxidative phosphorylation, which impaired the formation of ATP. The resulting cell death was not blocked by MPT (mitochondrial permeability transition) inhibitors (Debio 025 or bongkrekic acid). Thus pCramoll and rCramoll promote PC-3 cell death through calcium signaling, leading to mitochondrial collapse. This work provides more insights into the action of pCramoll and rCramoll against cancer cells. These lectins represent valuable tools for biomedical research.
来自毛蟹爪兰种子的凝集素已显示出体内抗肿瘤作用的潜力，然而其作用机制尚未得到阐明。在此，我们评估了来自毛蟹爪兰的天然（pCramoll）和重组（rCramoll）凝集素对人前列腺腺癌（PC-3）细胞的抗肿瘤作用。采用MTT法和膜联蛋白V/碘化丙啶染色分析PC-3细胞的活力。分别使用荧光探针（MitoSox Red、Fura 2-AM和番红O）评估pCramoll或rCramoll对线粒体超氧化物产生、胞质游离钙浓度和线粒体膜电位的影响。pCramoll和rCramoll以剂量依赖性方式降低PC-3细胞的活力。两种凝集素均增加了线粒体超氧化物的生成以及胞质钙的浓度。这些变化导致氧化磷酸化减少，从而损害了ATP的形成。由此导致的细胞死亡未被线粒体通透性转换（MPT）抑制剂（Debio 025或硼酸）阻断。因此，pCramoll和rCramoll通过钙信号传导促进PC-3细胞死亡，导致线粒体崩溃。这项工作为pCramoll和rCramoll对癌细胞的作用提供了更多见解。这些凝集素是生物医学研究的宝贵工具。
