Antitumor effects of disulfiram/copper complex in the poorly-differentiated nasopharyngeal carcinoma cells via activating ClC-3 chloride channel

Publication date: December 2019Source: Biomedicine &Pharmacotherapy, Volume 120Author(s): Xiao Xu, Jingkui Xu, Chongyu Zhao, Xiuying Hou, Mengjia Li, Liwei Wang, Lixin Chen, Yehui Chen, Linyan Zhu, Haifeng YangAbstractThe enhancement of the anticancer activity by disulfiram (DSF) chelated with copper (DSF/Cu2+) has been investigated recently, while the underlying molecular mechanisms still need to be fully elucidated. Chloride channel-3 (ClC-3) is over-expressed in a variety of cancers and involves multiple tumor biological events. However, whether the over-expression of ClC-3 in tumor cells affects the sensitivity of anti-tumor drugs remains unclear. Here, we showed that the involvement of ClC-3 chloride channel in the selective cytotoxicity of DSF/Cu2+ in the poorly-differentiated nasopharyngeal carcinoma. The EC50 of DSF alone and DSF/Cu2+ in activating the Cl− channel were 95.36 μM and 0.31 μM in the CNE-2Z cells, respectively. DSF/Cu2+ exhibited a positive correlation between the induction of the Cl− currents and the inhibition of cell proliferation. DSF/Cu2+ increased the ClC-3 protein expression and induced the cell apoptosis. Cl− channel blockers, NPPB and DIDS, and ClC-3 siRNA partially inhibited the cell apoptosis, and depleted the Cl− currents induced by DSF/Cu2+ in CNE-2Z cells. However, these effects could not be observed in the normal nasopharyngeal epithelium NP69-SV40 T cells. In vivo, the transplanted human nasopharynge...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research

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Abstract The enhancement of the anticancer activity by disulfiram (DSF) chelated with copper (DSF/Cu2+) has been investigated recently, while the underlying molecular mechanisms still need to be fully elucidated. Chloride channel-3 (ClC-3) is over-expressed in a variety of cancers and involves multiple tumor biological events. However, whether the over-expression of ClC-3 in tumor cells affects the sensitivity of anti-tumor drugs remains unclear. Here, we showed that the involvement of ClC-3 chloride channel in the selective cytotoxicity of DSF/Cu2+ in the poorly-differentiated nasopharyngeal carcinoma. The EC50 o...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
Abstract Nasopharyngeal carcinoma (NPC) is the most common primary malignancy that originates from the nasopharynx. Some regulatory networks involved in nasopharyngeal carcinoma have been reported, but the relevant genes have not been fully identified. We have used mRNA microarray to identify differential expression genes between NPC tissues and adjacent normal tissues. Then high-content shRNA screening was carried out to screen the genes that may control proliferation in nasopharyngeal carcinoma. Cell proliferation was monitored by MTT assays and Celigo image cytometry in vitro and subcutaneous transplantation mo...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
In conclusion, baicalein could inhibit the growth and proliferation of human nasopharyngeal carcinoma cells, change their cell cycle, and induce apoptosis. Baicalein also effectively limits both CNE1- and CNE2-transplanted tumors in nude mice. Downregulation of Bcl-xl and Mcl-1 proteins and upregulation of Bax and Bad may be involved in the mechanism. PMID: 31053182 [PubMed - in process]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: This study may throw light on the treatment of NPC and may help improve the prognosis of patients with NPC. PMID: 30899390 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Rationale: Hepatocellular carcinoma (HCC) is the fifth most common cancer and third leading cause of cancer-related deaths worldwide. Nasopharyngeal metastasis of hepatocellular carcinoma is very rare. This is the first report of posttransplantation nasopharyngeal metastasis. Patient concerns: A 45-year-old man with a history of hepatitis B related hepatocellular carcinoma (HCC) in the right segment of the liver received an orthotopic liver transplant. Two year after the transplantation, he suffered from severe headache, and head contrast enhanced CT scans did not show clues for brain or skull metastasis. Then he deve...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
lncRNA CASC2/miR‑18a‑5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8. Oncol Rep. 2018 Dec 19;: Authors: Miao WJ, Yuan DJ, Zhang GZ, Liu Q, Ma HM, Jin QQ Abstract Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non‑coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
CONCLUSION: These results suggest that it is feasible to generate highly-reactive EBV-specific T cells from human lymph node tissue using the methodology compatible with good manufacturing practice (GMP). In contrast to VST cells derived from peripheral blood, increased expression of CD28 and IL-2 on lymph node derived EBV reactive cells may indicate a superior capacity to survive, expand in vivo and eradicate EBV-driven disease upon adoptive transfer.Figure 1. Characterization of lymph node derived EBV reactive T cells.A) Expanded T cells from Blood (BL), iliac lymph node (iLN), mesenteric lymph node (MLN), and spleen (Sp...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research
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