scholarly journals A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O-α-L-Arabinosyl Oleanolic Acid) Isolated fromSchumacheria castaneifoliaVahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sameera R. Samarakoon ◽  
Meran K. Ediriweera ◽  
Chukwumaobim Daniel Uzochukwuwulu Nwokwu ◽  
Chamara Janaka Bandara ◽  
Kamani H. Tennekoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Oleanolic Acid ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Cytotoxic Effects

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated fromSchumacheria castaneifoliain non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression ofBax, p53, and survivingenes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation ofBaxandp53and downregulation ofsurvivinin NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

Radix Tetrastigma Inhibits the Non-Small Cell Lung Cancer via Bax/Bcl-2/Caspase-9/Caspase-3 Pathway

2021 ◽  
pp. 1-13
Author(s):  
Yonglu Li ◽  
Yaxuan Wang ◽  
Xin Yu ◽  
Ting Yu ◽  
Xiaodong Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Caspase 9

scholarly journals Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

scholarly journals Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

2018 ◽  
Vol 48 (4) ◽  
pp. 1433-1442 ◽  
Author(s):  
Jie Min ◽  
Hua Shen ◽  
Wang Xi ◽  
Qing Wang ◽  
Liang Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Caffeic Acid ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Caspase 9 ◽  
Anti Cancer

Background/Aims: Caffeic acid (CA) is known to possess multiple biological activities including anti-cancer activities. However, the molecular mechanisms underlying these activities in non-small-cell lung cancer (NSCLC) cells are not fully understood. We attempted to clarify whether CA could enhance paclitaxel (PTX)-induced cytotoxicity in H1299 cells. Methods: First, we tested the cytotoxic effects in both H1299 cells and normal human Bease-2b cells by cell proliferation experiments. Next, we use Annexin V/propidium iodide apoptosis analysis and flow cytometric analysis to investigate apoptosis and cell cycle arrest under the treatments mentioned above. To further pinpoint changes in apoptosis, we tested the caspase-associated apoptotic pathway, which involves the activities of caspase-3 and caspase-9. Moreover, apoptosis-related proteins and MAPK pathway proteins were examined by western blot. An H1299 xenograft nude mice model was used to further evaluate the tumor-suppressing effects of CA and PTX in vivo. Results: Combination treatment with low-dose CA and PTX decreased the proliferation of NSCLC H1299 cells but not normal Beas-2b cells. Flow cytometry showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. Caspase-3 and caspase-9 activities were both increased after CA treatment. Furthermore, CA increased the PTX-induced activation of Bax, Bid, and downstream cleaved PARP, and phosphorylation of extracellular signal regulated kinase1/2 and c-Jun NH2-terminal protein kinase1/2. An in vivo tumor-suppression assay demonstrated that CA and PTX combined treatment exerted a more effective suppressive effect on tumor growth in H1299 xenografts without causing significant adverse effects. Conclusions: Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.

scholarly journals Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Long ◽  
Jia-Hang Su ◽  
Bin Liang ◽  
Li-Li Su ◽  
Shu-Juan Jiang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Small Cell ◽  
Normal Lung ◽  
Specific Gene ◽  
Small Cell Lung ◽  
Cancer Subtypes ◽  
Gene Modules

Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

scholarly journals Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1α and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 126 ◽  
Author(s):  
Christophe Deben ◽  
Vanessa Deschoolmeester ◽  
Jorrit De Waele ◽  
Julie Jacobs ◽  
Jolien Van den Bossche ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Mutant P53 ◽  
Small Cell Lung ◽  
Hypoxic Conditions

The compound APR-246 (PRIMA-1MET) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228Q331* cell line, and not in the wild type A549 and mutant NCI-H1975R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228Q331* cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transcription targets under hypoxia. APR-246 was able to overcome hypoxia-induced cisplatin resistance in NCI-H2228Q331* cells in a synergistic manner without affecting mutant p53Q331* transcriptional activity, but significantly depleting total glutathione levels more efficiently under hypoxic conditions. Synergism was dependent on the presence of mutant p53Q331* and the induction of reactive oxygen species, with depletion of one or the other leading to loss of synergism. Our data further support the rationale of combining APR-246 with cisplatin in NSCLC, since their synergistic interaction is retained or enforced under hypoxic conditions in the presence of mutant p53.

A phase I study of weekly topotecan and vinorelbine in recurrent lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17140-17140
Author(s):  
M. A. Beldner
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase I Study ◽  
Single Agent ◽  
Small Cell ◽  
Fixed Dose ◽  
Small Cell Lung ◽  
Cytotoxic Effects

17140 Background: Topotecan is a topoisomerase I (topo I) inhibitor that directs cytotoxic effects by stabilizing the topo I-DNA complex. Alone, topotecan has shown activity in extensive small cell lung cancer (SCLC). Vinorelbine is a vinca alkaloid, which interacts with tubulin and disrupts microtubule function exhibiting cytotoxic effects, and has demonstrated activity in both non-small cell lung cancer (NSCLC) and SCLC. The rationale for using the agents in combination therapy is based upon their single agent activity and published preclinical data demonstrating synergy with topo I inhibitors and mitotic spindle poisons. Previous trials using topotecan weekly demonstrated less myelosuppression and equivalent anti-tumor activity. In this phase I study, we evaluated the safety profile of escalating doses of topotecan and a fixed dose of vinorelbine. Methods: Patients (pts) with recurrent NSCLC or SCLC were enrolled. Vinorelbine was delivered as 20mg/m2 on days 1 and 8, every 21 days. Topotecan was initiated at 2mg/m2 given on the same days. If there was no dose limiting toxicity (DLT) in each 3 person cohort, then topotecan was incrementally increased by 0.5mg/m2. Tolerability was assessed prior to each cycle. Responses were assessed after two cycles. Pts were taken off study for disease progression or unacceptable toxicities. Results: To date 12 pts have been enrolled (10 NSCLC, 2 extensive SCLC). Average ECOG performance status was 0–1 (11 pts 92%). Patients were heavily pretreated, this representing on average 2nd to 4th line therapy. Cohorts 1–3 had no DLT. In each cohort there were dose delays for grade 2 and 3 neutropenia and thrombocytopenia. Cohort 4 enrolled 3 pts with a DLT of grade 4 neutropenia observed in 1 pt. Nonmyeloid toxicities included nausea (42%), fatigue (33%), and constipation (17%). In cohorts 1–3, no CRs or PRs were seen. SD was observed in 6 pts (67%), with a median duration of 11 weeks. Response rates for cohort 4 are not yet assessed. Conclusion: Results of this ongoing phase I trial indicate that weekly vinorelbine and topotecan x 2 every three weeks was fairly well tolerated with grade 4 neutropenia being the primary DLT. The best response achieved in assessable pts was SD. Once the MTD has been established, a phase II study examining this regimen in advanced SCLC and NSCLC will be performed. No significant financial relationships to disclose.

A systems pathology model for predicting overall survival in patients with refractory, advanced non-small cell lung cancer (NSCLC) treated with gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18065-18065
Author(s):  
M. J. Donovan ◽  
A. Kotsianti ◽  
V. Bayer-Zubek ◽  
D. Verbel ◽  
M. Clayton ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cyclin D1 ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Support Vector ◽  
Small Cell Lung

18065 Background: The abundant expression of the epidermal growth factor receptor (EGFR) in a variety of solid tumors including non-small cell lung cancer (NSCLC), head and neck, breast, colon and brain has made it an attractive target for various selective molecular therapeutics, including the tyrosine kinase inhibitor gefitinib. The recent evidence of activating mutations in EGFR combined with clinical - demographic features has suggested that subgroups of patients with NSCLC are most likely to respond to selective therapies. We sought to determine whether the integration of clinical variables, tumor morphometry and quantitative protein profiles using support vector machines could identify a set of features which predicts overall survival in patients with NSCLC treated with gefitinib. Methods: We analyzed tumor samples from 109 patients with advanced refractory NSCLC treated with gefitinib. Formalin fixed, paraffin embedded tissue samples were evaluated with the following assays: Hematoxylin and Eosin image morphometry, EGFR DNA mutation analysis, EGFR protein immunohistochemistry and quantitative immunofluorescence with the following antibodies: CK18, Ki67, Caspase 3 activated, cd34, EGFR, phosphorylated-EGFR, phosphorylated-ERK, phosphorylated-AKT, PTEN, Cyclin D1, phosphorylated-m-TOR, PI3-K, VEGF, KDR (VEGFR2) and phosphorylated KDR. A predictive model was developed using support vector regression for censored data. Results: 4 of 87 patients had tyrosine kinase domain mutations in exons 19, 20 or 21. Utilizing 51 patients with complete data profiles (i.e. clinical, image morphometry and immunofluorescence), a model predicting overall survival was developed with a concordance index of 0.74. Poor performance status, poorly differentiated histology by morphometry and increased levels of activated caspase 3, phosphorylated KDR (VEGFR2) and cyclin D1 were associated with reduced survival. Conclusion: The integration of clinical, imaging and biomarker data identified a set of features which were associated with a more aggressive disease phenotype and resulted in overall poor survival. [Table: see text]

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