Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

Duan, Lincan; Shen, Hongmei; Zhao, Genming; Yang, Runxiang; Cai, Xiaoyan; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

doi:10.1016/j.bbrc.2014.03.047

Cited by 87 publications

(52 citation statements)

References 24 publications

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“…The most common type of lung cancer is non-small cell lung cancer (NSCLC) and its 5-year survival rate is < 15% 2 . Although extensive research has been carried out, the pathological process of lung cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Lin

et al. 2018

Cancer Biology & Medicine

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Objective:Long non-coding RNAs (lncRNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lncRNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1 (LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study. Methods:Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction (qPCR). Hematoxylin and eosin (HE) staining, qPCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines. Results:Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta (LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin. Conclusions:We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.

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Section: Introductionmentioning

confidence: 99%

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Lin

et al. 2018

Cancer Biology & Medicine

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“…1,3,7,8 Although some publications have speculated that DSF and copper form a complex, 3,9,10 studies in vitro and in vivo show that DSF is reduced to form a copper-binding ligand. 11,12 Since DSF has been used clinically for over 60 years, the pharmacokinetic (PK) properties of the drug have been explored in depth.…”

Section: Introductionmentioning

confidence: 99%

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Wehbe¹,

Anantha²,

Shi³

et al. 2017

IJN

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Copper diethyldithiocarbamate (Cu(DDC) 2 ) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC) 2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC) 2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC) 2 formulation prepared through a method that involves synthesis of Cu(DDC) 2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC) 2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4–11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC) 2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC) 2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC) 2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC (0−∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC) 2 formulation was subsequently evaluated in the MV-4–11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC) 2 formulation in vivo.

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“…1 To date, its treatment is still highly dependent on chemotherapy, in which platinum-based chemotherapy is the standard first-line therapy for NSCLC patients. 2 Thus, there is an urgent need to develop novel effective chemotherapeutics to overcome the limited therapeutic efficacy and strong side effects in traditional treatment, thereby increasing the overall survival of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

Wang¹,

Yang²,

Han³

et al. 2017

IJN

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In this study, poly(lactic- co -glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.

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Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

Cited by 87 publications

References 24 publications

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

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