scholarly journals MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in H2O2-treated lung cancer cells via increased superoxide anion and glutathione depletion

2017 ◽  
Author(s):  
Woo Park
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Superoxide Anion ◽  
Lung Cancer Cells ◽  
Glutathione Depletion ◽  
Mapk Inhibitors

scholarly journals Tubulin acetylation enhances lung cancer resistance to paclitaxel-induced cell death through Mcl-1 stabilization

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Onsurang Wattanathamsan ◽  
Rawikorn Thararattanobon ◽  
Ratchanee Rodsiri ◽  
Pithi Chanvorachote ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Trichostatin A ◽  
Primary Lung Cancer ◽  
Lung Cancer Cells ◽  
Cancer Resistance ◽  
Apoptosis Resistance ◽  
Tubulin Acetylation ◽  
Cancer Aggressiveness

AbstractThe posttranslational modifications (PTMs) of microtubules have been reported to play an important role in cancer aggressiveness, including apoptosis resistance. In this study, we aimed to investigate the biological role of microtubule PTMs in the regulation of paclitaxel responsiveness. The acetylated tubulin (Ace-tub) level was strongly associated with paclitaxel sensitivity, as observed in patient-derived primary lung cancer cells and xenografted immunodeficient mice. We showed that paclitaxel-resistant H460 lung cancer cells, generated by a stepwise increase in paclitaxel, exhibited markedly increased tubulin acetylation and consequently acquired paclitaxel resistance. Upregulation of tubulin acetylation by overexpression of α-tubulin acetyltransferase 1 wild-type (αTAT1wt), an enzyme required for acetylation, or by treatment with trichostatin A (TSA), a histone deacetylase 6 (HDAC6) inhibitor, significantly attenuated paclitaxel-induced apoptosis. Investigation of the underlying mechanism revealed that the levels of antiapoptotic Mcl-1 appeared to increase in αTAT1wt-overexpressing and TSA-treated cells compared to control cells, whereas the levels of other antiapoptotic regulatory proteins were unchanged. On the other hand, decreased tubulin acetylation by αTAT1 RNA interference downregulated Mcl-1 expression in patient-derived primary lung cancer and paclitaxel-resistant lung cancer cells. A microtubule sedimentation assay demonstrated that Mcl-1 binds to microtubules preferentially at Ace-type, which prolongs the Mcl-1 half-life (T1/2). Furthermore, immunoprecipitation analysis revealed that polyubiquitination of Mcl-1 was extensively decreased in response to TSA treatment. These data indicate that tubulin acetylation enhances the resistance to paclitaxel-induced cell death by stabilizing Mcl-1 and protecting it from ubiquitin–proteasome-mediated degradation.

A synthetic 2,3-diarylindole induces cell death via apoptosis and autophagy in A549 lung cancer cells

2016 ◽  
Vol 26 (9) ◽  
pp. 2119-2123 ◽  
Author(s):  
Thanya Rukkijakan ◽  
Lukana Ngiwsara ◽  
Kriengsak Lirdprapamongkol ◽  
Jisnuson Svasti ◽  
Nared Phetrak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
A549 Lung

Biological Effects of125I Seeds Radiation on A549 Lung Cancer Cells: G2/M Arrest and Enhanced Cell Death

2014 ◽  
Vol 32 (6) ◽  
pp. 209-217 ◽  
Author(s):  
Ang Qu ◽  
Hao Wang ◽  
Jinna Li ◽  
Junjie Wang ◽  
Jingjia Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Biological Effects ◽  
Lung Cancer Cells ◽  
A549 Lung

scholarly journals Antidepressant Drug Enhanced Trail Receptor-2 Expression and Sensitized Lung Cancer Cells to Trail-Induced Apoptosis via Inhibition of Autophagic Flux

2020 ◽  
Author(s):  
K.M.A. Zinnah ◽  
Jae-Won Seol ◽  
Sang-Youel Park
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Antidepressant Drug ◽  
Lung Cancer Cells ◽  
Autophagic Flux ◽  
Trail Receptor ◽  
Treatment Needs ◽  
Induced Apoptosis ◽  
Autophagy Inhibition

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

scholarly journals ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί

2021 ◽  
Vol 22 (22) ◽  
pp. 12287
Author(s):  
Jeon-Soo Lee ◽  
Young Eun Choi ◽  
Sunshin Kim ◽  
Ji-Youn Han ◽  
Sung-Ho Goh
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Therapeutic Effects ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tki

(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in more than half of the patients receiving EGFR TKI therapy. In addition to targeting new mutations with next-generation therapeutics, it is necessary to find an alternative target to overcome the challenges associated with resistance. (2) Methods: To identify potential alternative targets in patients with NSCLC undergoing targeted therapy, putative targets were identified by transcriptome profiling and validated for their biological and therapeutic effects in vitro and in vivo. (3) Results: ELF3 was found to be differentially expressed in NSCLC, and ELF3 knockdown significantly increased cell death in K-Ras mutant as well as in EGFR L858R/T790M mutation harboring lung cancer cells. We also found that auranofin, an inhibitor of protein kinase C iota (PKCί), a protein upstream of ELF3, effectively induced cell death. (4) Conclusions: Our study suggests that blocking ELF3 is an effective way to induce cell death in NSCLC with K-Ras and EGFR T790M/L858R mutations and thus advocates the use of auranofin as an effective alternative drug to overcome EGFR TKI resistance.

MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level

2010 ◽  
Vol 29 (7) ◽  
pp. 607-614 ◽  
Author(s):  
Yong Hwan Han ◽  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Proteasome Inhibitor ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Oxygen Species ◽  
A549 Lung

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC50 of approximately 20 μM at 24 hours. DNA flow cytometric analysis indicated that 0.5 ∼ 30 μM MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 μM MG132 also induced apoptosis, as evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; Δψm). The intracellular ROS levels including O2•- were strongly increased in 10 or 30 μM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 μM MG132-treated cells. Furthermore, 10 or 30 μM MG132 increased mitochondrial O2•- level but 0.1, 0.5 or 1 μM MG132 decreased that. In addition, 10 or 30 μM MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.

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