Long-Term Nitric Oxide Exposure Enhances Lung Cancer Cell Migration

Nitric oxide (NO) found in the vicinity of lung cancer cells may play a role in the regulation of cancer cell behaviors. To explore the possible effects of NO on cell motility, human lung cancer cells were exposed to nontoxic concentrations of NO for 0–14 days, and the migratory characteristics of the cells were determined. The present study found that long-term treatment with NO significantly enhanced cell migration in a dose- and time-dependent manner. Furthermore, we found that the increased migratory action was associated with the increased expression of caveolin-1 (Cav-1), which in turn activated the focal adhesion kinase (FAK) and ATP-dependent tyrosine kinase (Akt) pathways. Notably, the NO-treated cells exhibited an increased number of filopodia per cell, as well as an increase in the levels of cell division cycle 42 (Cdc42) protein. Together, these results indicate that extended NO exposure has a novel effect on cell migration through a Cav-1-dependent mechanism, a finding that strengthens our understanding of cancer biology.

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Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells

Cell Communication and Signaling ◽

10.1186/s12964-021-00763-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiaopeng Li ◽

Guilin Ma ◽

Wenjie Guo ◽

Ning Mu ◽

Yingying Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Molecular Mechanism ◽

Cancer Cell ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Lung Cancer Cell ◽

Cell Protrusion

Abstract Background Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive. Methods Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal. Results Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form. Conclusion Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy.

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Isoorientin Decreases Cell Migration via Decreasing Functional Activity and Molecular Expression of Proton-Linked Monocarboxylate Transporters in Human Lung Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x20500111 ◽

2020 ◽

Vol 48 (01) ◽

pp. 201-222

Author(s):

Hsu-Kai Huang ◽

Shin-Yi Lee ◽

Shu-Fen Huang ◽

Yu-San Lin ◽

Shih-Chi Chao ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Lung Adenocarcinoma ◽

Cell Viability ◽

Cancer Cells ◽

Functional Activity ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells

Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pHi) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pHi was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pHi was 7.47, and isoorientin (1–300[Formula: see text][Formula: see text]M) inhibited functional activity of MCT concentration-dependently (up to [Formula: see text]%). Pretreatment with isoorientin (3–100[Formula: see text][Formula: see text]M) for 24[Formula: see text]h, MCT activity and cell migration were significantly inhibited ([Formula: see text]% and [Formula: see text]%, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.

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Persistent effects of pair bonding in lung cancer cell growth in monogamous Peromyscus californicus

eLife ◽

10.7554/elife.64711 ◽

2021 ◽

Vol 10 ◽

Author(s):

Asieh Naderi ◽

Elham Soltanmaohammadi ◽

Vimala Kaza ◽

Shayne Barlow ◽

Ioulia Chatzistamou ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Nude Mice ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Lung Cancer Cell ◽

Peromyscus Californicus ◽

Pair Bonds ◽

The Impact

Epidemiological evidence suggests that social interactions and especially bonding between couples influence tumorigenesis, yet whether this is due to lifestyle changes, homogamy (likelihood of individuals to marry people of similar health), or directly associated with host-induced effects in tumors remains debatable. In the present study, we explored if tumorigenesis is associated with the bonding experience in monogamous rodents at which disruption of pair bonds is linked to anxiety and stress. Comparison of lung cancer cell spheroids that formed in the presence of sera from bonded and bond-disrupted deer mice showed that in monogamous Peromyscus polionotus and Peromyscus californicus, but not in polygamous Peromyscus maniculatus, the disruption of pair bonds altered the size and morphology of spheroids in a manner that is consistent with the acquisition of increased oncogenic potential. In vivo, consecutive transplantation of human lung cancer cells between P. californicus, differing in bonding experiences (n = 9 for bonded and n = 7 for bond-disrupted), and nude mice showed that bonding suppressed tumorigenicity in nude mice (p<0.05), suggesting that the protective effects of pair bonds persisted even after bonding ceased. Unsupervised hierarchical clustering indicated that the transcriptomes of lung cancer cells clustered according to the serum donors’ bonding history while differential gene expression analysis pointed to changes in cell adhesion and migration. The results highlight the pro-oncogenic effects of pair-bond disruption, point to the acquisition of expression signatures in cancer cells that are relevant to the bonding experiences of serum donors, and question the ability of conventional mouse models to capture the whole spectrum of the impact of the host in tumorigenesis.

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Corrigendum to “Long-Term Nitric Oxide Exposure Enhances Lung Cancer Cell Migration”

BioMed Research International ◽

10.1155/2015/310636 ◽

2015 ◽

Vol 2015 ◽

pp. 1-1

Author(s):

Arpasinee Sanuphan ◽

Preedakorn Chunhacha ◽

Varisa Pongrakhananon ◽

Pithi Chanvorachote

Keyword(s):

Nitric Oxide ◽

Lung Cancer ◽

Cell Migration ◽

Cancer Cell ◽

Cancer Cell Migration ◽

Lung Cancer Cell

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CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling pathways related with cell migration and suppresses metastasis of A549 human lung cancer cells

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2013.08.043 ◽

2013 ◽

Vol 23 (20) ◽

pp. 5609-5613 ◽

Cited By ~ 19

Author(s):

Min Jeong Ku ◽

Jong Woo Park ◽

Byung Jun Ryu ◽

Young-Jin Son ◽

Seong Hwan Kim ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Signaling Pathways ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Sequential Inactivation ◽

Ck2 Inhibitor

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Morphological Changes in H1299 Human Lung Cancer Cells Following Millimeter-Wave Irradiation

10.20944/preprints202003.0439.v1 ◽

2020 ◽

Author(s):

Konstantin Komoshvili ◽

Tzippi Beker ◽

Jacob Levitan ◽

Asher Yahalom ◽

Ayan Barbora ◽

...

Keyword(s):

Lung Cancer ◽

Side Effects ◽

Cancer Cells ◽

Human Lung ◽

Morphological Changes ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Physical Parameters ◽

Dependent Manner ◽

Human Lung Cancer Cells

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm2, investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term stress responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcome associated side effects. Adaptation of the experimental parameters of this study in clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSLC)

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Cell autonomous angiotensin II signaling controls the pleiotropic functions of oncogenic K-Ras

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015188 ◽

2020 ◽

pp. jbc.RA120.015188

Author(s):

Daniela Volonte ◽

Morgan Sedorovitz ◽

Victoria E. Cespedes ◽

Maria L. Beecher ◽

Ferruccio Galbiati

Keyword(s):

Lung Cancer ◽

Angiotensin Ii ◽

Cancer Cells ◽

Lung Tumor ◽

Tumor Formation ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Dependent Manner ◽

Ang Ii ◽

Normal Cells

Oncogenic K-Ras (K-RasG12V) promotes senescence in normal cells but fuels transformation of cancer cells after the senescence barrier is bypassed. The mechanisms regulating this pleiotropic function of K-Ras remain to be fully established and bear high pathological significance. We find that K-RasG12V activates the angiotensinogen (AGT) gene promoter and promotes AGT protein expression in a Kruppel Like Factor 6 (KLF6)-dependent manner in normal cells. We show that AGT is then converted to angiotensin II (Ang II) in a cell-autonomous manner by cellular proteases. We show that blockade of the Ang II receptor type 1 (AT1-R) in normal cells inhibits oncogene-induced senescence (OIS). We provide evidence that the oncogenic K-Ras-induced synthesis of Ang II and AT1-R activation promote senescence through caveolin-1-dependent and NOX2-mediated oxidative stress. Interestingly, we find that expression of AGT remains elevated in lung cancer cells but in a KLF6-independent and High Mobility Group AT-Hook 1 (HMGA1)-dependent manner. We show that Ang II-mediated activation of the AT1-R promotes cell proliferation and anchorage-independent growth of lung cancer cells through a STAT3-dependent pathway. Finally, we find that expression of AGT is elevated in lung tumors of K-RasLA2-G12D mice, a mouse model of lung cancer, and human lung cancer. Treatment with the AT1-R antagonist losartan inhibits lung tumor formation in K-RasLA2-G12D mice. Together, our data provide evidence of the existence of a novel cell-autonomous and pleiotropic Ang II-dependent signaling pathway through which oncogenic K-Ras promotes OIS in normal cells while fueling transformation in cancer cells.

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Emodin, isolated and characterized from an endophytic fungus Polyporales sp., induces apoptotic cell death in human lung cancer cells through the loss of mitochondrial membrane potential

The Journal of Phytopharmacology ◽

10.31254/phyto.2017.6506 ◽

2017 ◽

Vol 6 (5) ◽

pp. 288-292

Author(s):

Refaz Ahmad Dar ◽

◽

Rabiya Majeed ◽

Abid Ali sheikh ◽

Shakeel-u Rehman ◽

...

Keyword(s):

Lung Cancer ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Endophytic Fungus ◽

Mitochondrial Membrane ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Close Relative ◽

Dependent Manner

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a Chinese herbal anthraquinone that exhibits numerous biological activities, such as antitumor, antibacterial, antiinflammatory, and immunosuppressive. From an endophytic fungus, a close relative of Polyporales sp., found in association with Rheum emodi, Wall. ex Meissn a compound (Rz) was isolated and characterizedby different spectroscopic techniques (1H-NMR, 13CNMR, 2D-NMR, and HRMS). The compound (Rz) displayed a range of cytotoxicities against different human cancer cell lines like THP-1(Leukemia), A549 (Lung), NCI-H322 (lung) and Colo-205(colon) at a concentration of 70 and 100 µM. The compound had strong anticancer activity by arresting the cell cycle at G1 and G2/M phase and loss of mitochondrial membrane potential in A-549 lung cancer cells in concentration dependent manner. The study suggests that emodin induced anticancer effects may have novel therapeutic applications for the treatment of lung cancer.

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