Induction of Apoptosis and Growth Arrest in Human Breast Carcinoma Cells by a Snake (Walterinnesia aegyptia) Venom Combined With Silica Nanoparticles: Crosstalk Between Bcl2 and Caspase 3
Induction of Apoptosis and Growth Arrest in Human Breast Carcinoma Cells by a Snake (Walterinnesia aegyptia) Venom Combined With Silica Nanoparticles: Crosstalk Between Bcl2 and Caspase 3
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DOI：
10.1159/000341446
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Badr, Gamal
中科院分区：
文献类型：
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作者：
Al-Sadoon, Mohamed K.;Abdel-Maksoud, Mostafa A.;Badr, Gamal
我们最近发现，从埃及瓦林尼西亚提取的蛇毒（WEV）单独或与二氧化硅纳米颗粒（WEV+NP）组合，增强小鼠免疫细胞的增殖，同时降低人乳腺癌细胞株（MDA-MB-231）的增殖。然而，这种毒液如何诱导乳腺癌细胞生长停滞的分子机制尚未研究。在此背景下，我们扩展了我们的研究，以评估WEV和WEV+NP对人乳腺癌细胞系MDA-MB-231和MCF-7的抗肿瘤潜力，以及它们对非致瘤性正常乳腺上皮细胞（MCF-10）的影响。在这些细胞系中，单独的WEV和WEV+NP的IC 50值分别测定为50 ng/ml和20 ng/ml。有趣的是，在这些浓度下，毒液不影响正常MCF-10细胞的活力，并且单独用NP处理所有这些细胞系不影响它们的活力。使用Annexin-V结合试验和流式细胞术分析，我们发现WEV与NP的组合强烈诱导MDA-MB-231和MCF-7癌细胞的凋亡，而对正常MCF-10细胞没有显著影响。此外，我们还发现WEV+NP能降低MDA-MB-231和MCF-7细胞Bcl 2的表达，增强caspase 3的活化。最重要的是，WEV+ NP处理的乳腺癌细胞，而不是正常的MCF-10细胞，表现出显著的（P
We recently demonstrated that the snake venom extracted from Walterinnesia aegyptia (WEV) either alone or combined with silica nanoparticles (WEV+NP) enhanced the proliferation of mice immune cells and simultaneously decreased the proliferation of human breast carcinoma cell line (MDA-MB-231). However, the molecular mechanism of how this venom induced growth arrest of breast cancer cells has not been studied. In this context, we extended our study to evaluate the anti-tumor potential of WEV and WEV+NP on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of WEV alone and WEV+NP in these cell lines were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal MCF-10 cells and treatment of all these cell lines with NP alone did not affect their viability. Using annexin-V binding assay followed by flow cytometry analysis, we found that combination of WEV with NP strongly induced apoptosis in MDA-MB-231 and MCF-7 cancer cells without significant effect on normal MCF-10 cells. Furthermore, we found that WEV+NP decreased the expression of Bcl2 and enhanced the activation of caspase 3 in MDA-MB-231 and MCF-7 cells. Most importantly, WEV+NP-treated breast cancer cells, but not normal MCF-10 cells, exhibited a significant (P