Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.
Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.
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DOI：
10.1038/srep38992
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发表时间：
2016-12-15
影响因子：
4.6
通讯作者：
Hashim NM
中科院分区：
文献类型：
--
作者：
Fani S;Kamalidehghan B;Lo KM;Nigjeh SE;Keong YS;Dehghan F;Soori R;Abdulla MA;Chow KM;Ali HM;Hajiaghaalipour F;Rouhollahi E;Hashim NM
在本研究中，我们检测了希夫碱络合物、[N-(3，5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV)氯化物和C1对MDAMB-231细胞和从MDAMB-231细胞来源的乳腺癌干细胞的细胞毒作用。化合物C1的急性毒性试验表明，对大鼠无细胞毒性作用。用吖啶橙/碘化丙啶(AO/PI)染色的荧光显微镜研究和使用Annexin V探针的流式细胞术分析证实了C1处理的MDA-MB-231细胞发生了凋亡。化合物C1在处理后的MDA-MB-231细胞中引发细胞内活性氧(ROS)的产生和乳酸脱氢酶(LDH)的释放。细胞组学高含量筛选(HCS)分析显示，处理后的MDA-MB-231细胞有内在途径的诱导，发光实验显示caspase9和3/7活性显著增加。此外，流式细胞仪分析显示，化合物C1可诱导处理后的MDA-MB-231细胞G0/G1期停滞。实时定量聚合酶链式反应和免疫印迹分析显示Bax蛋白表达上调，而Bcl2和HSP70蛋白表达下调。此外，本研究还揭示了化合物C1对乳腺CSCs的抑制作用及其对Wnt/β-catenin信号通路的抑制作用。我们的结果证明了化合物C1对乳腺癌细胞和衍生的乳腺癌干细胞的化疗特性，这表明该化合物的抗癌能力应该在临床上进行评估。
In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.
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影响因子：
4.8
作者：
Ibrahim, Mohamed Yousif;Hashim, Najihah Mohd;Ali, Hapipah Mohd
通讯作者：
Ali, Hapipah Mohd
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1186/bcr1530
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fantozzi A;Christofori G
通讯作者：
Christofori G
影响因子：
5.1
作者：
Arulselvan, Palanisamy;Subramanian, Sorimuthu Pillai
通讯作者：
Subramanian, Sorimuthu Pillai
影响因子：
--
作者：
Kanagesan, S.;Hashim, M.;Ahsanul, K.
通讯作者：
Ahsanul, K.