scholarly journals Estrogen and cigarette sidestream smoke particulate matter exhibit ERα-dependent tumor-promoting effects in lung adenocarcinoma cells

2017 ◽  
Vol 313 (3) ◽  
pp. L477-L490 ◽  
Author(s):  
Lun-Cheng Kuo ◽  
Li-Chuan Cheng ◽  
Chia-Huei Lee ◽  
Chun-Ju Lin ◽  
Pei-Yu Chen ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Lung Adenocarcinoma ◽  
Secondhand Smoke ◽  
Estrogenic Activity ◽  
Granzyme B ◽  
Growth Factor Receptor ◽  
Dependent Manner ◽  
Sidestream Smoke ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Estrogen and secondhand smoke are key risk factors for nonsmoking female lung cancer patients who frequently have lung adenocarcinoma and show tumor estrogen receptor α (ERα) expression. We speculated that estrogen and secondhand smoke might cause harmful effects via ERα signaling. Our results showed that 17β-estradiol (E2), the primary form of endogenous estrogen, exacerbated proliferation, migration, and granzyme B resistance of lung adenocarcinoma cells in an ERα-dependent manner. Cigarette sidestream smoke particulate matter (CSSP), the major component of secondhand smoke, could activate ERα activity dose dependently in human lung adenocarcinoma cells. The estrogenic activity of CSSP was abolished by an ERα-selective antagonist. CSSP regulated the nuclear entry, phosphorylation, and turnover of ERα similarly to E2. Furthermore, CSSP enhanced E2-stimulated ERα activity and Ser118 phosphorylation even when ERα became saturated with E2. Activation of ERα by CSSP required GSK3β activity, but not involving polycyclic aromatic hydrocarbons, reactive oxygen species, calcium, epidermal growth factor receptor, and PI3K/Akt. Although CSSP possessed cytotoxicity, ERα-expressing cells grew and migrated faster than nonexpressing cells on recovery from CSSP exposure as observed in E2-pretreated cells. Knockdown of ERα by siRNA diminished E2- and CSSP-stimulated cell migration. Twenty-one genes, including SERPINB9, were identified to be upregulated by both E2 and CSSP via ERα. Increased SERPINB9 expression was accompanied with increased resistance to granzyme B-mediated apoptosis. This study demonstrates that estrogen has ERα-dependent tumor-promoting activity. CSSP acts like estrogen and shows a potential to enhance estrogen-induced ERα action.

scholarly journals 17α-Ethynylestradiol and 4-Nonylphenol Stimulate Lung Adenocarcinoma Cells Production in Xenoestrogenic Way

2018 ◽  
Author(s):  
Chia-Hung Sun ◽  
Jou-Chun Chou ◽  
Kuan-Po Chao ◽  
Hsian-Chi Chang ◽  
Fu-Kong Lieu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Air Pollutants ◽  
Estrogenic Activity ◽  
Growth Factor Receptor ◽  
Adenocarcinoma Cells ◽  
Epidermal Growth ◽  
Lung Adenocarcinoma Cells ◽  
First Time ◽  
Female Lung Cancer

Lung cancer has been the leading cause of cancer death in the world. In addition to smoking, estrogen is supposed to play an important role in the lung cancer development because women have a higher proportion of adenocarcinoma than men. In the environment, there are many metabolites and wastes that mimic human estrogen structurally and functionally. As an oral contraceptive, 17α-ethynylestradiol (EE2) is released to wastewater after being utilized. Moreover, 4-nonylphenol (NP) exiting in the petrochemical products and air pollutants has estrogenic activity. In our study, 17β-estradiol (E2), EE2, and NP are administered to stimulate A549 male lung adenocarcinoma cells and H1435 female lung adenocarcinoma cells. The results demonstrate that EE2 and NP stimulate A549 and H1435 cells proliferation in a dose- and time-dependent trend. Both estrogen receptor α and β are activated simultaneously during these processes. Up-regulation of epidermal growth factor receptor (EGFR) and ERK expression is involved in response to estrogens. In conclusion, we first time report that EE2 and NP exert biotoxic effect to stimulate the proliferation of both male and female lung cancer cells in a dose- and time- response manner. New challenges from environmental hormones to lung cancer deserved further investigation.

scholarly journals Influence of Autophagy Inhibition on Lung Adenocarcinoma Cell Migration and Invasion Ability, and Efficacy of Gefitinib

2021 ◽  
Vol 20 ◽  
pp. 153303382110490
Author(s):  
Ying Liu ◽  
Yun Du
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Malignant Tumors ◽  
Growth Factor Receptor ◽  
Scratch Test ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Autophagy Inhibition

An increasing number of studies have emphasized the role of autophagy in cancer cell metastasis and treatment of malignant tumors. Autophagy inhibitors have been widely used in combination therapies to treat advanced malignancies. Several lung adenocarcinoma cells harbor epidermal growth factor receptor (EGFR) gene mutations, and EGFR tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of lung adenocarcinoma. However, a number of lung adenocarcinoma tumors do not respond or develop resistance to EGFR TKIs. The aim of the present study was to explore the effect of autophagy inhibition on the biological behavior of lung adenocarcinoma cells. In addition, whether autophagy inhibition increases the efficacy of gefitinib in lung adenocarcinoma was investigated. The activation of autophagy was inhibited via the reduction of the expression of ATG5 in A549, H1975 and HCC827 cells. ATG5 knockdown using ATG5 siRNA partially suppressed the LC3B-II expression, decreased the LC3B-I/II conversion rate and enhanced the P62 expression. Cell scratch test and Transwell assay showed that the inhibition of autophagy could impair the migration and invasion ability of cells. These studies suggested that autophagy may play a pro-survival role in lung adenocarcinoma.

scholarly journals Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

2020 ◽  
Author(s):  
Zimple Kurlawala ◽  
Kumar Saurabh ◽  
Rain Dunaway ◽  
Parag P. Shah ◽  
Leah J. Siskind ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Human Lung Cancer ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

AbstractUbiquilin proteins (UBQLNs) are involved in diverse cellular processes like ERAD (endoplasmic reticulum associated degradation), autophagy, apoptosis and epithelial to mesenchymal transition. UBQLNs interact with a variety of substrates, including cell surface receptors, transcription factor regulators, proteasomal machinery proteins, and transmembrane proteins. Additionally, previous work from our lab shows that UBQLN1 interacts with IGFR family members (IGF1R, IGF2R, INSR) and this interaction regulates the activity and proteostasis of IGFR family members. Here, we examined regulation of UBQLN1 with Epidermal Growth Factor Receptor (EGFR) in lung adenocarcinoma cells. Loss of UBQLN1 occurs at high frequency in human lung cancer patient samples and we have shown that loss of UBQLN1 is capable altering processes involved in cell proliferation, migration, invasion and epithelial to mesenchymal transition in lung adenocarcinoma cell lines. Here, we present data that loss of UBQLN1 resulted in increased turnover of total EGFR, whilst increasing the relative amount of active EGFR in lung adenocarcinoma cells, especially in the presence of its ligand EGF. Furthermore, loss of UBQLN1 led to a more invasive cell phenotype as manifested by increased proliferation, migration and speed of movement of these lung adenocarcinoma cells. Taken together, UBQLN1 regulates expression and stability of IGFRs and EGFR, members of the receptor tyrosine kinase family of proteins in lung cancer cells.

scholarly journals Santamarine Inhibits NF-κB Activation and Induces Mitochondrial Apoptosis in A549 Lung Adenocarcinoma Cells via Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xuefeng Wu ◽  
Hua Zhu ◽  
Jingzhe Yan ◽  
Muhammad Khan ◽  
Xiuyan Yu
Keyword(s):  
Oxidative Stress ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Molecular Mechanism ◽  
Dependent Manner ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
A549 Lung

Santamarine (STM), a sesquiterpene lactone component of Magnolia grandiflora and Ambrosia confertiflora, has been shown to possess antimicrobial, antifungal, antibacterial, anti-inflammatory, and anticancer activities. However, no study has yet been conducted to investigate the molecular mechanism of STM-mediated anticancer activity. In the present study, we found that STM inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells through induction of oxidative stress. STM induces oxidative stress by promoting reactive oxygen species (ROS) generation, depleting intracellular glutathione (GSH), and inhibiting thioredoxin reductase (TrxR) activity in a dose-dependent manner. Further mechanistic study demonstrated that STM induces apoptosis by modulation of Bax/Bcl-2 expressions, disruption of mitochondrial membrane potential, activation of caspase-3, and cleavage of PARP in a dose-dependent manner. Moreover, STM inhibited the constitutive and inducible translocation of NF-κBp65 into the nucleus. IKK-16 (I-κB kinase inhibitor) augmented the STM-induced apoptosis, indicating that STM induces apoptosis in A549 cells at least in part through NF-κB inhibition. Finally, STM-induced apoptosis and expressions of apoptosis regulators were effectively inhibited by thiol antioxidant N-acetyl-L-cysteine (NAC), indicating that STM exerts its anticancer effects mainly through oxidative stress. To the best of our knowledge, this is the first report providing evidence of anticancer activity and molecular mechanism of STM.

scholarly journals Andrographolide Induces Noxa-Dependent Apoptosis by Transactivating ATF4 in Human Lung Adenocarcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Junqian Zhang ◽  
Chunjie Li ◽  
Li Zhang ◽  
Yongqing Heng ◽  
Tong Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Human Lung ◽  
High Dose ◽  
Dependent Manner ◽  
Human Lung Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis

Lung adenocarcinoma is the most common pathological type of lung cancer with poor patient outcomes; therefore, developing novel therapeutic agents is critically needed. Andrographolide (AD), a major active component derived from the traditional Chinese medicine (TCM) Andrographis paniculate, is a potential antitumor drug, but the role of AD in lung adenocarcinoma remains poorly understood. In the present study, we demonstrated that AD inhibited the proliferation of broad-spectrum lung cancer cell lines in a dose-dependent manner. Meanwhile, we found that a high dose of AD induced Noxa-dependent apoptosis in human lung adenocarcinoma cells (A549 and H1299). Further studies revealed that Noxa was transcriptionally activated by activating transcription factor 4 (ATF4) in AD-induced apoptosis. Knockdown of ATF4 by small interfering RNA (siRNA) significantly diminished the transactivation of Noxa as well as the apoptotic population induced by AD. These results of the present study indicated that AD induced apoptosis of human lung adenocarcinoma cells by activating the ATF4/Noxa axis and supporting the development of AD as a promising candidate for the new era of chemotherapy.

scholarly journals Thapsigargin Induces Apoptosis by Impairing Cytoskeleton Dynamics in Human Lung Adenocarcinoma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Fei Wang ◽  
Da-zhong Liu ◽  
Hao Xu ◽  
Yi Li ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Human Lung ◽  
A549 Cells ◽  
Dependent Manner ◽  
Human Lung Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Cytoskeletal Dynamics ◽  
Lung Adenocarcinoma Cells ◽  
Dose Dependent

The objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by depletion of lumenal calcium stores and show potential to induce cell death. The effects of thapsigargin on the apoptosis in A549 cells were assayed by Hoechst staining. Moreover, the F-actin staining by Rhodamine-phalloidin and RhoA antibody for cytoskeleton organizations were applied to A549 cells. To confirm the impairment of cytoskeletal dynamics treated with thapsigargin, western blots were applied to analyze the protein levels of p-Cofilin-1 (Ser3), Cofilin-1, and pPaxillin (Tyr118), as well as RhoA and pS6 (S240/244). Results suggest that thapsigargin may induce cell death in A549 cells with a time- and dose-dependent manner. The F-actin fibers and RhoA signals are also reduced with a time- and dose-dependent manner by thapsigargin treatment. The phosphorylation forms of Cofilin-1 and paxillin are attenuated by 1 μM thapsigargin treatment for 24 h. These alternations may be caused by the inhibition of of mTORC1 activities (indicated by pS6 (Ser240/244)) and RhoA pathways after thapsigargin treatment. The present findings highlight important roles of calcium entry in cytoskeleton organization and apoptosis in human lung adenocarcinoma cells and will help to set a stage to the clinical treatment of cancer cell metastasis.

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