The therapeutic effects of vitamin C on lung cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18523-e18523
Author(s):  
Ashorne Krithiesh Mahenthiran ◽  
Gurusingham Sitta Sittampalam ◽  
Raj Somasundaram ◽  
Sanjit Nirmalanandhan

e18523 Background: In this in-vitro study, we determined the effects of vitamin C (Ascorbic acid), an essential vitamin, on two different lung cancer cell lines (H358 – Bronchioalveolar Carcinoma and A549 – Epithelial Lung carcinoma) and two normal lung cell lines as control groups (MRC5 – Human lung fibroblast tissue and NL20 – Lung epithelial cells). Methods: In the study, the four cell lines were treated with Vitamin C starting from 0.005 molar concentrations and serially diluted down 1:3 ratios to low nM concentrations. All experiments were carried out in a period of 4 weeks. The viability of the cell lines after the drug treatment was measured using a MTS cell proliferation assay. Results: The study was inconclusive since the viability of both normal and lung cells were equally affected under the experimental conditions except that the dosage of vitamin C that killed 50% of H358 was at a slightly lower concentration than the dosage of vitamin C that killed 50% of the normal lung cells. These results show that there is a possibility of an optimal dosage that will only harm cancerous cells in specific cancers and not on all cancers. Conclusions: These results were inconclusive; probably due to the fact that experimental conditions in this in-vitro study may not be appropriate to show the effects of Vitamin C on lung cancer cells. It is possible that lower dosages of vitamin C may still kill cancer cells selectively, and may also be more effective in cancers in ther tissues. Despite these drawbacks, in-vivo experiments in animal models with lung cancer may show the benefits of Vitamin C in combination with standard of care cancer drugs. Future experiments will examine combinations experiments in vitro and in animals to study the beneficial effects of Vitamin C.

2019 ◽  
Vol 97 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Yufu Tang ◽  
Lijian Wu ◽  
Mingjing Zhao ◽  
Guangdan Zhao ◽  
Shitao Mao ◽  
...  

Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behavior of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at the G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. The migration and invasiveness of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that the epithelial–mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing, as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist, and vimentin. In addition, we found that SNHG4 silencing induced up-regulation of miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20074-e20074
Author(s):  
Yangyang Fu ◽  
Xiaoying Huang ◽  
Liangxing Wang

e20074 Background: Carboxypepidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Previous study discovered that CPA4 may participate in cell growth and differentiation of prostate epithelial cells. Meanwhile, CPA4 is a printed gene and thought to be involved in prostate cancer aggressiveness. As is reported, CPA4 was increased in NSCLC tissues compared to normal lung tissues and high expression of CPA4 was correlated with poor prognosis of NSCLC patients. However, the role of CPA4 play in lung tumorigenesis is still unclear. Methods: We examined the mRNA and protein expression level of CPA4 via real-time PCR and immunohistochemistry in NSCLC tissues and adjacent tissues. Growth assays both in vitro and in vivo were performed to elucidate the role of CPA4 may play in lung cancer and Fluorescence Activated Cell Sorter was conducted to uncover the putative mechanism. Results: CPA4 expression was increased both in mRNA and protein levels in NSCLC tissues compared to adjacent tissues. MTT and colony formation assays showed that downregulation of CPA4 in H1299 and A549 cells inhibited lung cancer cells proliferation. We further confirmed this result by using cellomics and celligo. Depleting CPA4 also suppressed tumor growth in mice. Mechanically, we found that suppressing CPA4 expression in lung cancer cells could induce apoptosis and G1 arrest. We supposed that CPA4 expression may be associated with caspase family and it needs further studies. Conclusions: Collectively, we demonstrate that decreased CPA4 inhibits NSCLC proliferation via inducing apoptosis and G1 arrest.


2020 ◽  
Vol 295 (25) ◽  
pp. 8470-8479
Author(s):  
Van T. Hoang ◽  
Katherine Nyswaner ◽  
Pedro Torres-Ayuso ◽  
John Brognard

Identifying additional mitogen-activated protein kinase (MAPK) pathway regulators is invaluable in aiding our understanding of the complex signaling networks that regulate cellular processes, including cell proliferation and survival. Here, using in vitro kinase assays and by expressing WT or kinase-dead MAPK kinase kinase 19 (MAP3K19) in the HEK293T cell line and assessing activation of the extracellular signal–regulated kinase (ERK) and JUN N-terminal kinase (JNK) signaling pathways, we defined MAP3K19 as a novel regulator of MAPK signaling. We also observed that overexpression of WT MAP3K19 activates both the ERK and JNK pathways in a panel of cancer cell lines. Furthermore, MAP3K19 sustained ERK pathway activation in the presence of inhibitors targeting the RAF proto-oncogene Ser/Thr protein kinase (RAF) and MAPK/ERK kinase, indicating that MAP3K19 activates ERK via a RAF-independent mechanism. Findings from in vitro and in-cell kinase assays demonstrate that MAP3K19 is a kinase that directly phosphorylates both MAPK/ERK kinase (MEK) and MAPK kinase 7 (MKK7). Results from an short-hairpin RNA screen indicated that MAP3K19 is essential for maintaining survival in KRAS-mutant cancers; therefore, we depleted or inhibited MAP3K19 in KRAS-mutant cancer cell lines and observed that this reduces viability and decreases ERK and JNK pathway activation. In summary, our results reveal that MAP3K19 directly activates the ERK and JNK cascades and highlight a role for this kinase in maintaining survival of KRAS-mutant lung cancer cells.


Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.


2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.


Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 79
Author(s):  
Hengju Ge ◽  
Di Zhang ◽  
Muran Shi ◽  
Xiaoyuan Lian ◽  
Zhizhen Zhang

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.


Sign in / Sign up

Export Citation Format

Share Document