scholarly journals Escape from Therapy-Induced Accelerated Cellular Senescence in p53-Null Lung Cancer Cells and in Human Lung Cancers

2005 ◽  
Vol 65 (7) ◽  
pp. 2795-2803 ◽  
Author(s):  
Rachel S. Roberson ◽  
Steven J. Kussick ◽  
Eric Vallieres ◽  
Szu-Yu J. Chen ◽  
Daniel Y. Wu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cellular Senescence ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Lung Cancers

scholarly journals Epigenetic Silencing of TMEM176A Activates ERK Signaling in Human Lung Cancer

2020 ◽  
pp. 1-11
Author(s):  
Liming Hu ◽  
Fuyou Zhou ◽  
Hongxia Li ◽  
James G Herman ◽  
Liming Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Promoter Region ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Erk Signaling ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
H460 Cells ◽  
Partially Methylated

Background: The function of TMEM176A in human lung cancer remains to be elucidated. Materials & Methods: Nine cell lines and 123 cases of lung cancers were employed. Results: TMEM176A was highly expressed in H727 cells, reduced expression was observed in A549, H446 and H460 cells, loss of expression was found in H157, H1563, H358, H1299 and H23 cells. TMEM176A was unmethylated in H727 cells, partially methylated in A549, H446 and H460 cells, and fully methylated in H157, H1563, H358, H1299 and H23 cells. Loss of/reduced expression of TMEM176A is correlated to promoter region methylation. Restoration of TMEM176A expression was induced by 5-AZA-2- deoxycytidine in complete methylated cells, increased expression of TMEM176A was observed in partially methylated cells. These results suggest that TMEM176A is regulated by promoter region methylation in lung cancer cells. TMEM176A was methylated in 53.66% (66/123) of non-small cell lung cancers (NSCLCs) samples. Reduced expression of TMEM176A was associated with promoter region methylation in 40 cases of matched primary NSCLCs and adjacent tissue samples (P<0.05). TMEM176A expression induced cell apoptosis, inhibited colony formation, cell proliferation, migration and invasion. Conclusion: Methylation of TMEM176A activated ERK signaling in lung cancer cells. TMEM176A suppressed human lung cancer cell xenograft growth in mice.

scholarly journals Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers

2018 ◽  
Vol 115 (8) ◽  
pp. 1913-1918 ◽  
Author(s):  
Masanori Kawakami ◽  
Lisa Maria Mustachio ◽  
Lin Zheng ◽  
Yulong Chen ◽  
Jaime Rodriguez-Canales ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Dna Content ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Normal Lung ◽  
Lung Cancers ◽  
Centriole Duplication ◽  
Apoptotic Death

Polo-like kinase 4 (PLK4) is a serine/threonine kinase regulating centriole duplication. CFI-400945 is a highly selective PLK4 inhibitor that deregulates centriole duplication, causing mitotic defects and death of aneuploid cancers. Prior work was substantially extended by showing CFI-400945 causes polyploidy, growth inhibition, and apoptotic death of murine and human lung cancer cells, despite expression of mutated KRAS or p53. Analysis of DNA content by propidium iodide (PI) staining revealed cells with >4N DNA content (polyploidy) markedly increased after CFI-400945 treatment. Centrosome numbers and mitotic spindles were scored. CFI-400945 treatment produced supernumerary centrosomes and mitotic defects in lung cancer cells. In vivo antineoplastic activity of CFI-400945 was established in mice with syngeneic lung cancer xenografts. Lung tumor growth was significantly inhibited at well-tolerated dosages. Phosphohistone H3 staining of resected lung cancers following CFI-400945 treatment confirmed the presence of aberrant mitosis. PLK4 expression profiles in human lung cancers were explored using The Cancer Genome Atlas (TCGA) and RNA in situ hybridization (RNA ISH) of microarrays containing normal and malignant lung tissues. PLK4 expression was significantly higher in the malignant versus normal lung and conferred an unfavorable survival (P < 0.05). Intriguingly, cyclin dependent kinase 2 (CDK2) antagonism cooperated with PLK4 inhibition. Taken together, PLK4 inhibition alone or as part of a combination regimen is a promising way to combat lung cancer.

scholarly journals S-phase kinase-associated protein 2 positively controls mitotic arrest deficient 2 in lung cancer cells

2016 ◽  
Author(s):  
Tonghai Huang ◽  
Lin Yang ◽  
Guangsuo Wang ◽  
Guanggui Ding ◽  
Bin Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Spindle Assembly Checkpoint ◽  
Human Lung ◽  
Mitotic Arrest ◽  
S Phase ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
Protein Levels

Background. Mitotic arrest deficient 2 (Mad2) is a key component of spindle assembly checkpoint and overexpressed in human lung cancers, but the mechanism of the deregulation of Mad2 in lung cancer is largely unknown. We aim to investigate the regulation of Mad2 by S-phase kinase-associated protein 2 (Skp2) in human lung cancer cells. Methods. Human lung cancer A549 and NCI-H1975 cells were transfected with MAD2 and SKP2 siRNAs or plasmids to silence or overexpress MAD2 and SKP2. Flavopiridol and HLM006474 were used to inhibit cyclin dependent kinases (CDKs) and E2F1, respectively. mRNA and protein levels were determined by real-time PCR and Western blot, respectively. Cell cycle progression was assayed by flow cytometery. Results. Knockdown of Skp2 by siRNA decreased Mad2 mRNA and protein levels in A549 and NCI-H1299 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb). In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression, and prevented the increase of Mad2 expression by Skp2. Accordingly, silencing of either Mad2 or Skp2 impaired the mitosis arrest in response to nocadazole. Conclusion. SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway, suggesting that deregulation of Skp2 may lead to upregulation of Mad2 via enhancing the activity of CDKs in human lung cancers. Our findings may provide an explanation of the simultaneous upregulation of MAD2 and SKP2 in lung cancer and potential targets for the development of molecular targeted therapy for lung cancers.

scholarly journals S-phase kinase-associated protein 2 positively controls mitotic arrest deficient 2 in lung cancer cells

2016 ◽  
Author(s):  
Tonghai Huang ◽  
Lin Yang ◽  
Guangsuo Wang ◽  
Guanggui Ding ◽  
Bin Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Spindle Assembly Checkpoint ◽  
Human Lung ◽  
Mitotic Arrest ◽  
S Phase ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
Protein Levels

Background. Mitotic arrest deficient 2 (Mad2) is a key component of spindle assembly checkpoint and overexpressed in human lung cancers, but the mechanism of the deregulation of Mad2 in lung cancer is largely unknown. We aim to investigate the regulation of Mad2 by S-phase kinase-associated protein 2 (Skp2) in human lung cancer cells. Methods. Human lung cancer A549 and NCI-H1975 cells were transfected with MAD2 and SKP2 siRNAs or plasmids to silence or overexpress MAD2 and SKP2. Flavopiridol and HLM006474 were used to inhibit cyclin dependent kinases (CDKs) and E2F1, respectively. mRNA and protein levels were determined by real-time PCR and Western blot, respectively. Cell cycle progression was assayed by flow cytometery. Results. Knockdown of Skp2 by siRNA decreased Mad2 mRNA and protein levels in A549 and NCI-H1299 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb). In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression, and prevented the increase of Mad2 expression by Skp2. Accordingly, silencing of either Mad2 or Skp2 impaired the mitosis arrest in response to nocadazole. Conclusion. SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway, suggesting that deregulation of Skp2 may lead to upregulation of Mad2 via enhancing the activity of CDKs in human lung cancers. Our findings may provide an explanation of the simultaneous upregulation of MAD2 and SKP2 in lung cancer and potential targets for the development of molecular targeted therapy for lung cancers.

Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Lingyan Wang ◽  
Jiayun Hou ◽  
Minghuan Zheng ◽  
Lin Shi
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Retinoic Acid Receptor ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Inhibitory Effects ◽  
The Core ◽  
Human Lung Cancer Cells ◽  
Receptor Beta

Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the anti-tumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots.

EFFECTS OF OPIOIDS AND NICOTINE ON APOPTOSIS IN HUMAN LUNG CANCER CELLS

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 548-552
Author(s):  
Rhoda Maneckjee ◽  
Kathleen Dehen ◽  
John D. Minna
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation

2020 ◽  
Vol 20 (5) ◽  
pp. 372-381
Author(s):  
Yoshiaki Sato ◽  
Hironori Yoshino ◽  
Eichi Tsuruga ◽  
Ikuo Kashiwakura
Keyword(s):  
Lung Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Poly I:C ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells ◽  
Induced Apoptosis

Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface. Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR. Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed. Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression. Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.

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