The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells

Hour, Mann Jen; Yang, Jai Sing; Chen, Tai Lin; Chen, Kuan Tin; Kuo, Sheng Chu; Chung, Jing Gung; Lu, Chi‐Cheng; Chen, Chia Yi; Chuang, Yi Hsuan

doi:10.1016/j.ejmech.2011.03.059

Cited by 15 publications

(16 citation statements)

References 36 publications

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“…CH‐11 induces apoptosis in cell lines with a functionally active Fas . Previously, other authors observed caspase‐8 activation irrespective of whether or not chemotherapy‐induced apoptosis was dependent on the Fas activation . These different results are due to the fact that different mechanisms beyond Fas‐activation, can contribute to caspase‐8/caspase‐3 axis activation, probably in stimulus and/or cell type‐dependent manner.…”

Section: Discussionmentioning

confidence: 92%

“…Fas and FasL expression as well as their role in anti‐cancer drug‐induced apoptosis has been demonstrated in a number of cell lines from haematological malignancies and solid tumours …”

Section: Discussionmentioning

confidence: 99%

“…Fas and FasL expression as well as their role in anti-cancer drug-induced apoptosis has been demonstrated in a number of cell lines from haematological malignancies and solid tumours. [8][9][10][11][12] In a previous study, we found that gemcitabine increased the expression of functionally active Fas in three different NSCLC cell lines (H292 mucoepidermoid carcinoma, Colo699 adenocarcinoma and CorL23 large-cell carcinoma). 5 In the present study, we demonstrate that gemcitabine increases the expression of FasL in H292 cells, leading to an autocrine and/or paracrine death mechanism involving the Fas/FasL system-mediated caspase-8 and caspase-3 activation.…”

Section: Discussionmentioning

confidence: 99%

“…Upon anti‐cancer drug treatment, an up‐regulation of both Fas and FasL was observed in various tumour cell lines including Hodgkin's lymphoma, Ewing's sarcoma, colon cancer, small cell lung cancer, hepatoma, osteosarcoma and pancreatic cancer; triggering cell apoptosis via an autocrine/paracrine loop by Fas cross‐linking . Previous studies have also demonstrated that anti‐cancer drugs increase the sensitivity of various tumour cell lines including prostate, colon, bladder, pancreas and brain cancer cells, to Fas‐dependent killing by cytotoxic lymphocytes .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Upon anti-cancer drug treatment, an up-regulation of both Fas and FasL was observed in various tumour cell lines including Hodgkin's lymphoma, Ewing's sarcoma, colon cancer, small cell lung cancer, hepatoma, osteosarcoma and pancreatic cancer; triggering cell apoptosis via an autocrine/paracrine loop by Fas cross-linking. [8][9][10][11][12] Previous studies have also demonstrated that anti-cancer drugs increase the sensitivity of various tumour cell lines including prostate, colon, bladder, pancreas and brain cancer cells, to Fas-dependent killing by cytotoxic lymphocytes. [13][14][15][16] Although the expression and up-regulation of Fas and/or FasL by anti-cancer drugs and their role in tumour suppression are known phenomena, [17][18][19] the effects of gemcitabine on the Fas/FasL-system in NSCLC are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

et al. 2014

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SummaryGemcitabine is a chemotherapy agent commonly used in the treatment of non-small cell lung cancer (NSCLC) that has been demonstrated to induce apoptosis in NSCLC cells by increasing functionally active Fas expression. The aim of this study was to evaluate the Fas/Fas ligand (FasL) system involvement in gemcitabine-induced lung cancer cell killing. NSCLC H292 cells were cultured in the presence or absence of gemcitabine. FasL mRNA and protein were evaluated by real-time PCR, and by Western blot and flow cytometry, respectively. Apoptosis of FasL-expressing cells was evaluated by flow cytometry, and caspase-8 and caspase-3 activation by Western blot and a colorimetric assay. Cytotoxicity of lymphokine-activated killer (LAK) cells and malignant pleural fluid lymphocytes against H292 cells was analysed in the presence or absence of the neutralizing anti-Fas ZB4 antibody, by flow cytometry. Gemcitabine increased FasL mRNA and total protein expression, the percentage of H292 cells bearing membrane-bound FasL (mFasL) and of mFasL-positive apoptotic H292 cells, as well as caspase-8 and caspase-3 cleavage. Moreover, gemcitabine increased CH11-induced caspase-8 and caspase-3 cleavage and proteolytic activity. Cytotoxicity of LAK cells and pleural fluid lymphocytes was increased against gemcitabine-treated H292 cells and was partially inhibited by ZB4 antibody. These results demonstrate that gemcitabine: (i) induces up-regulation of FasL in lung cancer cells triggering cell apoptosis via an autocrine/paracrine loop; (ii) induces a Fas-dependent apoptosis mediated by caspase-8 and caspase-3 activation; (iii) enhances the sensitivity of lung cancer cells to cytotoxic activity of LAK cells and malignant pleural fluid lymphocytes, partially via Fas/FasL pathway. Our data strongly suggest an active involvement of the Fas/FasL system in gemcitabine-induced lung cancer cell killing.

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Section: Discussionmentioning

confidence: 92%

“…Fas and FasL expression as well as their role in anti‐cancer drug‐induced apoptosis has been demonstrated in a number of cell lines from haematological malignancies and solid tumours …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

et al. 2014

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Fe₃O₄ nanoparticle‐supported copper(I): magnetically recoverable and reusable catalyst for the synthesis of quinazolinones and bicyclic pyrimidinones

Lin

Wang

et al. 2012

Applied Organom Chemis

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A highly efficient, easily recoverable and reusable Fe3O4 magnetic nanoparticle‐supported Cu(I) catalyst has been developed for the synthesis of quinazolinones and bicyclic pyrimidinones. In the presence of supported Cu(I) catalyst (10 mol%), amidines reacted with substituted 2‐halobenzoic acids and 2‐bromocycloalk‐1‐enecarboxylic acids to generate the corresponding N‐heterocycle products in good to excellent yields at room temperature in DMF. In addition, the supported Cu(I) catalyst could be recovered at least 10 times without significant loss of its catalytic activity. Copyright © 2012 John Wiley & Sons, Ltd.

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2′‐Chloro‐4′‐aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G₂/M Cell Cycle Arrest and Apoptosis Triggers

Feng

Zhang

Tan

et al. 2012

Archiv der Pharmazie

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A series of 2'-chloro-4'-nitroflavone and 2'-chloro-4'-aminoflavone derivatives were synthesized by a convenient synthetic process. The in vitro anti-proliferation ability of these compounds was evaluated against hepatocarcinoma cells (HepG2), breast adenocarcinoma cells (MCF-7), and human chronic myelogenous leukemia cells (K562). Most of synthetic compounds possessed notable anti-proliferation activity against HepG2 cells and little activity against MCF-7 cells and K562 cells. In particular, compounds 4c and 4e exhibited high anti-proliferation activity against HepG2 cells with IC(50) at about 2.0 µM. Further toxicity screening toward normal human hepatocytes indicated that some compounds had low toxicity against normal liver cells, among which 4e displayed very weak effects on QSG7701 and HL7702 cells, with IC(50) values >100 and 50 µM, respectively. Compound 4c, with the best anti-proliferation activity in amino-substituted flavones (IC(50) = 2.0 µM), was selected for further evaluation of its effects on apoptosis and the cell cycle. HepG2 cells were exposed to this compound at 10 µM, which induced nuclear disassembly and DNA fragmentation. Flow cytometry analysis suggested that the population of apoptotic cells greatly increased in the 4c-treated HepG2 cells, and the cell cycle was arrested at the G(2)/M phase.

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The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells

Cited by 15 publications

References 36 publications

Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

Fe₃O₄ nanoparticle‐supported copper(I): magnetically recoverable and reusable catalyst for the synthesis of quinazolinones and bicyclic pyrimidinones

2′‐Chloro‐4′‐aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G₂/M Cell Cycle Arrest and Apoptosis Triggers

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The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells

Cited by 15 publications

References 36 publications

Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

Gemcitabine sensitizes lung cancer cells to Fas/FasL system‐mediated killing

Fe3O4 nanoparticle‐supported copper(I): magnetically recoverable and reusable catalyst for the synthesis of quinazolinones and bicyclic pyrimidinones

2′‐Chloro‐4′‐aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G2/M Cell Cycle Arrest and Apoptosis Triggers

Contact Info

Product

Resources

About

Fe₃O₄ nanoparticle‐supported copper(I): magnetically recoverable and reusable catalyst for the synthesis of quinazolinones and bicyclic pyrimidinones

2′‐Chloro‐4′‐aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G₂/M Cell Cycle Arrest and Apoptosis Triggers