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一种来自海洋海绵 Cinachyrella apion(Cal)的乳糖结合凝集素可诱导人宫颈腺癌细胞死亡。

A lactose-binding lectin from the marine sponge Cinachyrella apion (Cal) induces cell death in human cervical adenocarcinoma cells.

机构信息

Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.

Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.

出版信息

Mar Drugs. 2012 Apr;10(4):727-743. doi: 10.3390/md10040727. Epub 2012 Mar 28.

Abstract

Cancer represents a set of more than 100 diseases, including malignant tumors from different locations. Strategies inducing differentiation have had limited success in the treatment of established cancers. Marine sponges are a biological reservoir of bioactive molecules, especially lectins. Several animal and plant lectins were purified with antitumor activity, mitogenic, anti-inflammatory and antiviral, but there are few reports in the literature describing the mechanism of action of lectins purified from marine sponges to induce apoptosis in human tumor cells. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated with respect to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death in tumor cells. The antiproliferative activity of CaL was tested against HeLa, PC3 and 3T3 cell lines, with highest growth inhibition for HeLa, reducing cell growth at a dose dependent manner (0.5-10 µg/mL). Hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC(50) (10 µg/mL) for both trials and twice the IC(50) for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. Results showed that lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase and acting as both dependent and/or independent of caspases pathway. These results indicate the potential of CaL in studies of medicine for treating cancer.

摘要

癌症是一组超过 100 种疾病的统称,包括来自不同部位的恶性肿瘤。诱导分化的策略在治疗已确立的癌症方面取得的成功有限。海洋海绵是生物活性分子的生物库,尤其是凝集素。已经有几种具有抗肿瘤活性、有丝分裂原活性、抗炎和抗病毒活性的动物和植物凝集素被纯化,但文献中很少有描述从海洋海绵中纯化的凝集素诱导人肿瘤细胞凋亡的作用机制的报道。在这项工作中,评估了从海洋海绵 Cinachyrella apion(CaL)中纯化的凝集素的溶血、细胞毒性和抗增殖特性,以及诱导肿瘤细胞死亡的能力。CaL 的抗增殖活性在 HeLa、PC3 和 3T3 细胞系中进行了测试,对 HeLa 的生长抑制作用最强,以剂量依赖的方式降低细胞生长(0.5-10μg/mL)。使用两种试验的 IC50 浓度(10μg/mL)和流式细胞术分析的 IC50 浓度的两倍测试 CaL 的溶血活性和对外周血细胞的毒性,表明 CaL 对这些细胞没有毒性。为了评估 CaL 在 HeLa 细胞中引起细胞死亡的机制,我们进行了流式细胞术和 Western blot 分析。结果表明,凝集素可能通过促凋亡蛋白 Bax 激活细胞凋亡诱导细胞死亡,促进线粒体膜通透性、细胞周期停滞在 S 期,并作为 caspase 途径的依赖性和/或非依赖性发挥作用。这些结果表明 CaL 在癌症治疗医学研究中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/232d/3366672/03f7fa6a40e0/marinedrugs-10-00727-g001.jpg

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