Low Energy Proton Beam Induces Efficient Cell Killing in A549 Lung Adenocarcinoma Cells

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.

Download Full-text

Enhancing effect of connexin 32 gene on vinorelbine-induced cytotoxicity in A549 lung adenocarcinoma cells

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-006-0406-3 ◽

2007 ◽

Vol 60 (3) ◽

pp. 449-457 ◽

Cited By ~ 20

Author(s):

Hiromi Sato ◽

Keiko Fukumoto ◽

Sachio Hada ◽

Hiromi Hagiwara ◽

Eriko Fujimoto ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Connexin 32 ◽

Enhancing Effect ◽

Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

A549 Lung

Download Full-text

Dicentrine Potentiates TNF-α-Induced Apoptosis and Suppresses Invasion of A549 Lung Adenocarcinoma Cells via Modulation of NF-κB and AP-1 Activation

Molecules ◽

10.3390/molecules24224100 ◽

2019 ◽

Vol 24 (22) ◽

pp. 4100 ◽

Cited By ~ 6

Author(s):

Chanatip Ooppachai ◽

Pornngarm Limtrakul (Dejkriengkraikul) ◽

Supachai Yodkeeree

Keyword(s):

Lung Adenocarcinoma ◽

Transcriptional Activity ◽

A549 Cells ◽

Anticancer Activities ◽

Necrosis Factor Alpha ◽

Adenocarcinoma Cells ◽

Tnf Α ◽

Lung Adenocarcinoma Cells ◽

Induced Apoptosis ◽

A549 Lung

Numerous studies have indicated that tumor necrosis factor-alpha (TNF-α) could induce cancer cell survival and metastasis via activation of transcriptional activity of NF-κB and AP-1. Therefore, the inhibition of TNF-α-induced NF-κB and AP-1 activity has been considered in the search for drugs that could effectively treat cancer. Dicentrine, an aporphinic alkaloid, exerts anti-inflammatory and anticancer activities. Therefore, we investigated the effects of dicentrine on TNF-α-induced tumor progression in A549 lung adenocarcinoma cells. Our results demonstrated that dicentrine effectively sensitizes TNF-α-induced apoptosis in A549 cells when compared with dicentrine alone. In addition, dicentrine increases caspase-8, -9, -3, and poly (ADP-ribose) polymerase (PARP) activities by upregulating the death-inducing signaling complex and by inhibiting the expression of antiapoptotic proteins including cIAP2, cFLIP, and Bcl-XL. Furthermore, dicentrine inhibits the TNF-α-induced A549 cells invasion and migration. This inhibition is correlated with the suppression of invasive proteins in the presence of dicentrine. Moreover, dicentrine significantly blockes TNF-α-activated TAK1, p38, JNK, and Akt, leading to reduced levels of the transcriptional activity of NF-κB and AP-1. Taken together, our results suggest that dicentrine could enhance TNF-α-induced A549 cell death by inducing apoptosis and reducing cell invasion due to, at least in part, the suppression of TAK-1, MAPK, Akt, AP-1, and NF-κB signaling pathways.

Download Full-text