Abstract 5543: Elucidating the cytotoxic effects of taxol,camptothecin and Lobostemon fruticosus extracts on non-small cell lung cancer

2015 ◽  
Author(s):  
Lesetja Raymond Motadi ◽  
Lungile Ndlovu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cytotoxic Effects

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.

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.

scholarly journals Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1271
Author(s):  
Kuo-Yen Huang ◽  
Tong-Hong Wang ◽  
Chin-Chuan Chen ◽  
Yann-Lii Leu ◽  
Hsin-Jung Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Third Generation ◽  
Small Cell Lung ◽  
Cytotoxic Effects

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At present, there are no clear options for treating patients who acquire resistance to third-generation TKIs. The acquisition of the EGFR C797S mutation was shown to upregulate the expression of AXL, a receptor tyrosine kinase of the TAM (TYRO3-AXL-MER) family, and the suppression of AXL is effective in reducing the growth of NSCLC cells harboring EGFR C797S. As quercetin was recently shown to inhibit AXL, quercetin may be effective in treating NSCLC cells harboring the EGFR C797S mutation. In this work, the cytotoxic effects of quercetin and its ability to inhibit tumor growth were examined in TKI-resistant NSCLC cells harboring the EGFR C797S mutation. We demonstrated that quercetin exhibited potent cytotoxic effects on NSCLC cells harboring the EGFR C797S mutation by inhibiting AXL and inducing apoptosis. Quercetin inhibited the tumor growth of xenografted NSCLC cells harboring the EGFR C797S mutation and appeared to act synergistically with brigatinib to inhibit of tumor growth in vivo. In summary, herein, we revealed that quercetin is an effective inhibitor for the treatment of non-small-cell lung cancer harboring the EGFR C797S mutation.

scholarly journals Cytotoxic effects of pyrrolidine dithiocarbamate in small-cell lung cancer cells, alone and in combination with cisplatin

2014 ◽  
Vol 45 (4) ◽  
pp. 1749-1759 ◽  
Author(s):  
SHINICHI TAHATA ◽  
BO YUAN ◽  
HIDETOMO KIKUCHI ◽  
NORIO TAKAGI ◽  
TOSHIHIKO HIRANO ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Pyrrolidine Dithiocarbamate ◽  
Small Cell Lung ◽  
Cytotoxic Effects

FOXO1 and FOXO3a sensitize non-small-cell lung cancer cells to cisplatin-induced apoptosis independent of Bim

2020 ◽  
Vol 52 (12) ◽  
pp. 1348-1359
Author(s):  
Tianyu Sun ◽  
Jingge Zhang ◽  
Bo Deng ◽  
Xiaoqing Fan ◽  
Tan Long ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nuclear Accumulation ◽  
Akt Pathway ◽  
Small Cell Lung ◽  
Cytotoxic Effects ◽  
Cell Sensitivity ◽  
Response To Chemotherapy

Abstract Low sensitivity to chemotherapy has been a major challenge in the treatment of non-small-cell lung cancer (NSCLC). It is of great clinical significance to discover its mechanisms to improve cell sensitivity to chemotherapeutic drugs. The forkhead box subfamily O (FOXO) transcriptional factors are downstream factors of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and are reported to play pro-apoptotic roles in a variety of cells including NSCLC cells. But their roles and mechanisms in mediating cell response to chemotherapy remain to be discovered. We proposed that FOXO1 and FOXO3a may increase the sensitivity of NSCLC cells to cisplatin. Moreover, we presumed that LY294002, an inhibitor of the PI3K/AKT pathway, may enhance the cytotoxic effects of cisplatin through upregulating FOXO1 and FOXO3a. In the present study, we found that cisplatin initially increased the expressions and nuclear accumulation of FOXO1 and FOXO3a in NSCLC. Knockdown of FOXO1 and FOXO3a significantly decreased the cell sensitivity to cisplatin in vitro and in vivo. Moreover, inhibition of FOXO1 and FOXO3a attenuated cisplatin-induced cell apoptosis independent of Bim, a pro-apoptotic protein downstream of the FOXOs. Moreover, LY294002 synergistically increased the cytotoxic effects of cisplatin. Mechanistically, LY294002 increased the expressions and nuclear accumulation of FOXO1 and FOXO3a. Knockdown of FOXO1 and FOXO3a abrogated the enhancing effect of LY294002 on cisplatin. Taken together, our results suggested that FOXO1 and FOXO3a sensitize NSCLC cells to cisplatin and mediate the enhancing effects of LY294002 on cisplatin.

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