Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide

Liu, Shousheng; Xia, Liangping; Jiang, Chang; Chen, Ping; Wang, Xiaopai; Zhang, Bei; Zhao, Hong

doi:10.3892/ol.2017.7488

Cited by 5 publications

(5 citation statements)

References 42 publications

(37 reference statements)

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“…Western blot analysis was performed as previously reported (20). Total protein was extracted by radioimmunoprecipitation assay buffer (Sangon Biotech Co., Ltd.), and the concentration was determined by the bicinchoninic acid method.…”

Section: Methodsmentioning

confidence: 99%

“…Cell cycle analysis was performed as previously described (20). In brief, the NCI-H209 cells transfected with NSE siRNA-1 or control siRNA for 48 h were collected and fixed with 75% ice-cold ethanol, prior to being stored at −20°C for 3 h. Subsequently, the cells were centrifuged at 7,000 g at 37°C for 1 min, resuspended in 1 ml lysis/propidium iodide (PI) buffer (0.1% Triton X-100, 0.05 mg/ml PI and 1 mg/ml RNase A; Sigma-Aldrich; Merck KGaA), incubated at 37°C for 30 min and analyzed using a FACSCanto II flow cytometer (BD Biosciences) with FACSDiva software (version 4.1; BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

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Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

Liu

et al. 2019

Oncol Lett

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Neuron-specific enolase (NSE) is generally considered as a marker for diagnosis and evaluation of the response to therapy in small cell lung cancer (SCLC). However, the role of NSE in the progression of SCLC remains to be elucidated. In the present study, the functions of NSE in SCLC, in addition to the potential mechanisms, were investigated using a loss-of-function approach with NSE-targeting small interfering (si)RNA. The knockdown of NSE markedly decreased the proliferation of NCI-H209 cells, as indicated by MTT assay (P<0.05). Furthermore, the silencing of NSE resulted in the formation of smaller and fewer colonies compared with that in the control group (P<0.001). Flow cytometric analysis indicated that the silencing of NSE resulted in a decreased S-phase population among NCI-H209 cells (P<0.05). Transwell assay demonstrated that the silencing of NSE suppressed the migration of NCI-H209 cells (P<0.001). NCI-H209 cells transfected with NSE siRNA-1 or negative control were collected and the protein levels of metastasis-associated genes were detected using western blot analysis. The results indicated that the knockdown of NSE led to downregulation of the pro-metastatic gene vascular endothelial growth factor (VEGF; P<0.05) and the upregulation of metastasis suppressor genes NM23 and E-cadherin (P<0.05). Taken together, the results of the present study demonstrated that the silencing of NSE suppressed the migration, proliferation and colony formation ability of SCLC cells and decreased the S-phase population. In addition, the knockdown of NSE resulted in the upregulation of E-cadherin and NM23 and the downregulation of VEGF. Collectively, these results indicated that intracellular NSE may have an important role in the progression of SCLC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

Liu

et al. 2019

Oncol Lett

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“…Previous studies provided some insight into this concern. Silencing of autophagy-related ATG5 arrested cells in S phase [33], a phenotype similar to the cells that were treated with autophagy inhibitors CQ [34], suggesting a possibility that CUR5g-induced autophagy inhibition might contribute to S phase arrest in A549 cells. It has been reported that cisplatin facilitated cell cycle arrest in lung cancer cells [35,36].…”

Section: Discussionmentioning

confidence: 65%

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anti-cancer effects with cisplatin against non-small-cell lung cancer

Zhang

Chen

Shen

et al. 2022

Preprint

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Autophagy, a highly conserved degradation process of eukaryotic cells, has been proved to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anti-cancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.

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“…Previous studies provided some insight into this concern. Silencing of autophagy-related ATG5 arrested cells in S phase [ 33 ], a phenotype similar to the cells that were treated with autophagy inhibitors CQ [ 34 ], suggesting a possibility that CUR5g-induced autophagy inhibition might contribute to S phase arrest in A549 cells. It has been reported that cisplatin facilitated cell cycle arrest in lung cancer cells [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 97%

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer

Chen

Shen

et al. 2022

Cell Death Discov.

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Autophagy, a highly conserved degradation process of eukaryotic cells, has been proven to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anticancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.

show abstract

Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide

Cited by 5 publications

References 42 publications

Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anti-cancer effects with cisplatin against non-small-cell lung cancer

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer

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