scholarly journals Replication Study: Discovery and preclinical validation of drug indications using compendia of public gene expression data

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Irawati Kandela ◽  
Fraser Aird ◽  

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper “Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data“ (Sirota et al., 2011). Here we report the results of those experiments. We found that cimetidine treatment in a xenograft model using A549 lung adenocarcinoma cells resulted in decreased tumor volume compared to vehicle control; however, while the effect was in the same direction as the original study (Figure 4C; Sirota et al., 2011), it was not statistically significant. Cimetidine treatment in a xenograft model using ACHN renal cell carcinoma cells did not differ from vehicle control treatment, similar to the original study (Supplemental Figure 1; Sirota et al., 2011). Doxorubicin treatment in a xenograft model using A549 lung adenocarcinoma cells did not result in a statistically significant difference compared to vehicle control despite tumor volume being reduced to levels similar to those reported in the original study (Figure 4C; Sirota et al., 2011). Finally, we report a random effects meta-analysis for each result. These meta-analyses show that the inhibition of A549 derived tumors by cimetidine resulted in a statistically significant effect, as did the inhibition of A549 derived tumors by doxorubicin. The effect of cimetidine on ACHN derived tumors was not statistically significant, as predicted.

RSC Advances ◽  
2019 ◽  
Vol 9 (37) ◽  
pp. 21134-21138 ◽  
Author(s):  
Yu Mei Que ◽  
Xiao Qing Fan ◽  
Xiao Juan Lin ◽  
Xiao Li Jiang ◽  
Ping Ping Hu ◽  
...  

Size-dependent anti-invasiveness effect of AgNPs was determined using A549 lung adenocarcinoma cells. The 13 nm AgNPs can significantly inhibit the migration and invasion of A549 cells and induce the elevated level of ROS and NF-κB directed cell apoptosis.


FEBS Journal ◽  
2008 ◽  
Vol 275 (22) ◽  
pp. 5725-5732 ◽  
Author(s):  
Qiuxia He ◽  
Bin Huang ◽  
Jing Zhao ◽  
Yun Zhang ◽  
Shangli Zhang ◽  
...  

FEBS Letters ◽  
1998 ◽  
Vol 437 (1-2) ◽  
pp. 61-64 ◽  
Author(s):  
Fulu Bai ◽  
Takayoshi Matsui ◽  
Naoko Ohtani-Fujita ◽  
Yoshizumi Matsukawa ◽  
Yi Ding ◽  
...  

2018 ◽  
Vol 45 (3) ◽  
pp. 917-934 ◽  
Author(s):  
Fangqiong Li ◽  
Dongxiao Zhao ◽  
Suwen Yang ◽  
Juan Wang ◽  
Qin Liu ◽  
...  

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.


2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2096118
Author(s):  
Xudong Bai ◽  
Jin Tang

Myrcene, a natural olefinic hydrocarbon, possesses anti-inflammatory, analgesic, antibiotic, and antimutagenic properties, but its anticancer effect has not yet been elucidated. Hence, the present study was framed to investigate the molecular mechanism by which myrcene mediates the anticancer activity of A549 lung adenocarcinoma cells. In vitro, A549 lung cancer cells were cultured either with or without myrcene, and the effects on cellular metabolic activity, levels of reactive oxygen species (ROS), mitochondrial integrity, deoxyribonucleic acid (DNA) damage, and activity of caspases were analyzed. The study demonstrated that compared with control cells, myrcene induces cell death in a dose-dependent manner while inducing ROS levels. Further experiments revealed that the metabolic activity of the A549 lung adenocarcinoma cells was diminished with increased DNA damage and altered cellular integrity. In addition, increased activity of caspase-3 was also evidenced with reduced mitochondrial membrane potential synthesis in the myrcene-treated cells, which demonstrate that lung cancer cells experience signs of toxicity during myrcene treatment through the activation of the apoptosis mechanism via mitochondria-mediated cell death signaling and induction of oxidative stress. The results provide the first report on the evidence of anticancer activity and the possibility of a new drug that could be used for the treatment of lung cancer.


2007 ◽  
Vol 60 (3) ◽  
pp. 449-457 ◽  
Author(s):  
Hiromi Sato ◽  
Keiko Fukumoto ◽  
Sachio Hada ◽  
Hiromi Hagiwara ◽  
Eriko Fujimoto ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document