The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways
In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mec...
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2021
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oai:doaj.org-article:1ce259e40f98411ab96265dace113d852021-11-14T04:30:19ZThe endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways0753-332210.1016/j.biopha.2021.112360https://doaj.org/article/1ce259e40f98411ab96265dace113d852021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011446https://doaj.org/toc/0753-3322In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice.Lingyun ZhaoHongyun LiXin HuangTing LiuYi XinZhongqing XiaoWenfei ZhaoShaoyi MiaoJing ChenZengbei LiYang MiElsevierarticlePlatinum nanoclustersNon-small cell lung cancerCaveolin-mediated endocytosisMicropinocytosisCisplatin-resistantApoptosis mechanismTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112360- (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Platinum nanoclusters Non-small cell lung cancer Caveolin-mediated endocytosis Micropinocytosis Cisplatin-resistant Apoptosis mechanism Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
Platinum nanoclusters Non-small cell lung cancer Caveolin-mediated endocytosis Micropinocytosis Cisplatin-resistant Apoptosis mechanism Therapeutics. Pharmacology RM1-950 Lingyun Zhao Hongyun Li Xin Huang Ting Liu Yi Xin Zhongqing Xiao Wenfei Zhao Shaoyi Miao Jing Chen Zengbei Li Yang Mi The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| description |
In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice. |
| format |
article |
| author |
Lingyun Zhao Hongyun Li Xin Huang Ting Liu Yi Xin Zhongqing Xiao Wenfei Zhao Shaoyi Miao Jing Chen Zengbei Li Yang Mi |
| author_facet |
Lingyun Zhao Hongyun Li Xin Huang Ting Liu Yi Xin Zhongqing Xiao Wenfei Zhao Shaoyi Miao Jing Chen Zengbei Li Yang Mi |
| author_sort |
Lingyun Zhao |
| title |
The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| title_short |
The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| title_full |
The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| title_fullStr |
The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| title_full_unstemmed |
The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways |
| title_sort |
endocytic pathway of pt nanoclusters and their induced apoptosis of a549 and a549/cis cells through c-myc/p53 and bcl-2/caspase-3 signaling pathways |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/1ce259e40f98411ab96265dace113d85 |
| work_keys_str_mv |
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