Adenocarcinoma Cell
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2021 ◽  
Vol 11 ◽  
Xuan Lu ◽  
Ningning Kang ◽  
Xinxin Ling ◽  
Ming Pan ◽  
Wenjing Du ◽  

BackgroundFerroptosis is a newly generated regulatory cell death promoted by the accumulated lipid-based reactive oxygen species (ROS). Solute carrier family 7 member 11 (SLC7A11), the cystine/glutamate antiporter, is known as a ferroptosis executor that exhibits a positive correlation with carcinoma progression because of antioxidant function. Nonetheless, it is yet unclear on the understanding of ferroptosis regulation in lung cancer.MethodsDatabase, qRT-PCR, Western-blot (WB), and immunohistochemistry were utilized to determine SLC7A11 expression and function, as well as gene iron related to necrosis in clinical tissue specimens and cells; a ferroptosis inducer, inhibitors, and SLC7A11 lentivirus were used to confirm SLC7A11’s biological activity in cell viability, oxidative stress, lipid peroxidation, and iron ion enrichment in non-small cell lung cancer (NSCLC) in different cells; lentivirus was used to infect lung adenocarcinoma cell lines to acquire miR-27a-3p overexpression and knockdown cell lines, and to detect SLC7A11 level through qRT-PCR and WB. The influence of upregulated/downregulated miR-27a-3p on ferroptosis and other related biological characteristics of lung adenocarcinoma cell lines was detected.ResultsUpregulated SLC7A11 was shown in NSCLC patients and cells, and increased SLC7A11 had a relation to the poorly prognostic status of NSCLC patients. Besides, a novel miRNA, miR-27a-3p, was an essential modulator of ferroptosis via directly targeting SLC7A11 in NSCLC cells. Overexpressing miR-27a-3p led to SLC7A11 suppression via directly binding to its 3’-UTR, followed by the reduction of erastin-caused ferroptosis. In contrast, inhibited miR-27a-3p resulted in an increase in NSCLC cells’ sensitivity to erastin. Of importance, the accumulated lipid ROS and cell death of iron peptide mediated by anti-miR-27a-3p can be eliminated by impeding the glutamylation process. Our literature collectively uncovered that miR-27a-3p modulated ferroptosis by targeting SLC7A11 in NSCLC cells, illustrating the important role of miRNA in ferroptosis.ConclusionMiR-27a-3p modulates ferroptosis via targeting SLC7A11 in NSCLC cells, implying the significant role of miR-27a-3p/SLC7A11 in ferroptosis.

2021 ◽  
Vol 11 (10) ◽  
pp. 499
Ali Jason Saleh ◽  
Leen Othman ◽  
Michel Elchoueiry ◽  
Rita Ghanem ◽  
Samer Bazzi ◽  

Background: Yerba mate, a popular, tea-like beverage prepared from the dried leaves of Ilex paraguariensis, is widely consumed, and has several reported health benefits. Compared with other herbal teas, the effect of yerba mate on human cells in the context of cancer has not been extensively studied. The method of extraction of bioactive compounds from the yerba mate leaves plays an important role in its effect on cancer cells. Methods: In this study we assessed the viability, anti-proliferative, and apoptotic effect of the aqueous yerba mate extract, prepared using the same conditions employed for consumption, on different human colorectal cancer cell lines (Caco-2, HT-29, and HCT116) and on the non-tumorigenic human colon epithelial cell line (NCM460).Results: Cytotoxicity of aqueous yerba mate extract was studied and a dose-dependent decrease in viability was observed in all the tested cell lines. At 24 hrs., viability decreased to 19.7% with Caco-2 cells, 2.7% with HCT116, and 8.4% with HT-29 cells at a concentration of 4.8 mg/mL of yerba mate extract. The effect was less prominent on the NCM460 cell line where the viability of cells at the same concentration was 65.2%. Yerba mate extract also showed concentration-dependent anti-proliferative effects as determined by the WST-1 proliferation kit. IC50 values ranged between 0.22-0.69 mg/mL at 24 hr for cell lines tested. To study whether cell death was due to apoptosis, Caco-2 cells were stained with Annexin V-FITC assay and an increase in the percentage of late apoptotic Caco-2 cells was observed with yerba mate extract at 0.6-4.8 mg/mL. Cell cycle analysis using DNA content by flow cytometry showed an increase in the percentage of Caco-2 cells in the subG0/G1 phase and the G0/G1 phase after treatment with 2.4 mg/mL extract. Collectively, our data suggest that yerba mate aqueous extract exhibits an anti-proliferative effect on tested cell lines by inducing apoptosis.  Conclusions: Yerba mate aqueous extract exhibits a strong anti-proliferative activity against adenocarcinoma cell lines studied and constitutes a promising functional food adjuvant to anti-cancer therapy. Further work is needed to identify active components and mechanisms of action. Keywords: Aqueous extract, yerba mate, anti-proliferative activity, adenocarcinoma cell lines 

2021 ◽  
Vol 16 (10) ◽  
pp. 1934578X2110454
Sibel Kokturk ◽  
Fatma Kaya Dagistanli ◽  
Sibel Dogan ◽  
Emel Usta ◽  
Hatice Colgecen ◽  

Isoflavones have attracted much notice due to their health advantages; however, a comprehensive understanding of the effects of isoflavones on endometrium biology remains undiscovered. The expression and deficiency of leukemia inhibitory factor (LIF) and LIF receptor (LIFR) has been shown to be involved in multiple implantations failures in female infertility. Mechanisms implicated in the failure of implantations require further researches, thus our aim is to investigate the effect of the Trifolium pratense L. isoflavone extract with abundant formononetin content on implantation through assessing LIF and LIFR expressions. The Ishikawa cells were cultured with 20, 30, and 40 µg/mL concentrations of Trifolium pratense L. isoflavone extracts for 24 h and detected staining intensity of LIF and LIFR by immunocytochemistry and immunofluorescence staining using image analysis software. As compared with the control and 20 µg/mL Trifolium pratense L. groups, the staining intensity of LIF and LIFR in 30 and 40 µg/mL Trifolium pratense L. groups were significantly increased ( P < .0001). Our findings suggest that Trifolium pratense L. isoflavone extract may alter the endometrium expression of LIF and LIFR in the human endometrial adenocarcinoma cell line.

2021 ◽  
Wenzhong Peng ◽  
Jia Chen ◽  
Ruoxi He ◽  
Yongjun Tang ◽  
Juan Jiang ◽  

Abstract Background: Lung cancer is the most common cancer and one of the main causes of cancer-related deaths, and it manifests as metastatic disease in most cases. Considering frequent gene mutation and/or signaling deregulation in lung adenocarcinoma, identifying novel factors or agents targeting these signaling pathways might be promising strategies for lung adenocarcinoma therapy. Methods: GEO datasets were analyzed to identify differentially expressed genes (DEGs) in lung adenocarcinoma. The specific effects of candidate gene overexpression or knockdown on lung adenocarcinoma cell phenotypes were examined. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) are used to connect the genomic and functional information of DEGs. The dynamic effects of candidate gene and signaling pathway agonist on lung adenocarcinoma malignant behaviors were investigated. Finally, clinical lung adenocarcinoma and adjacent non-cancerous tissues were collected and the levels of candidate gene were examined in tissue samples.Results: Inhibitor of DNA binding 2 (ID2) was identified as an aberrantly downregulated gene in lung adenocarcinoma. ID2 overexpression suppressed lung adenocarcinoma cell viability, colony formation capacity, and migration. ID2 overexpression also reduced the protein levels of N-cadherin, MMP2, MMP9, and the phosphorylation of AKT and mTOR. The PI3K/AKT/mTOR signaling agonist exerted opposite effects on lung adenocarcinoma cells to those of ID2 overexpression, and partially reversed the effects of ID2 overexpression. In tissue samples, ID2 protein levels and mRNA expression were also downregulated compared with those in adjacent non-cancerous tissues. Conclusion: ID2 exerts its tumor-suppressive effects on lung adenocarcinoma cell malignant behaviors through inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. Restoring ID2 expression in lung adenocarcinoma cells might improve the curative effect of lung adenocarcinoma therapies.

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 956
Marine Jacquet ◽  
Eric Hervouet ◽  
Timothée Baudu ◽  
Michaël Herfs ◽  
Chloé Parratte ◽  

The pathway of selective autophagy, leading to a targeted elimination of specific intracellular components, is mediated by the ATG8 proteins, and has been previously suggested to be involved in the regulation of the Epithelial–mesenchymal transition (EMT) during cancer’s etiology. However, the molecular factors and steps of selective autophagy occurring during EMT remain unclear. We therefore analyzed a cohort of lung adenocarcinoma tumors using transcriptome analysis and immunohistochemistry, and found that the expression of ATG8 genes is correlated with that of EMT-related genes, and that GABARAPL1 protein levels are increased in EMT+ tumors compared to EMT- ones. Similarly, the induction of EMT in the A549 lung adenocarcinoma cell line using TGF-β/TNF-α led to a high increase in GABARAPL1 expression mediated by the EMT-related transcription factors of the SMAD family, whereas the other ATG8 genes were less modified. To determine the role of GABARAPL1 during EMT, we used the CRISPR/Cas9 technology in A549 and ACHN kidney adenocarcinoma cell lines to deplete GABARAPL1. We then observed that GABARAPL1 knockout induced EMT linked to a defect of GABARAPL1-mediated degradation of the SMAD proteins. These findings suggest that, during EMT, GABARAPL1 might intervene in an EMT-regulatory loop. Indeed, induction of EMT led to an increase in GABARAPL1 levels through the activation of the SMAD signaling pathway, and then GABARAPL1 induced the autophagy-selective degradation of SMAD proteins, leading to EMT inhibition.

2021 ◽  
Marina Saisana ◽  
S. Michael Griffin ◽  
Felicity E. B. May

Abstract Background Gastric adenocarcinoma is common and consequent mortality high. Presentation and mortality are increased in obese individuals, many of whom have elevated circulating insulin concentrations. High plasma insulin concentrations may promote, and increase mortality from, gastric adenocarcinoma. Tumour promotion activities of insulin and its receptor are untested in gastric cancer cells. Methods Tumour gene amplification and expression were computed from sequencing and microarray data. Associations with patient survival were assessed. Insulin-dependent signal transduction, growth, apoptosis and anoikis were analysed in metastatic cells from gastric adenocarcinoma patients and in cell lines. Receptor involvement was tested by pharmacological inhibition and genetic knockdown. RNA was analysed by RT-PCR and proteins by western transfer and immunofluorescence. Results INSR expression was higher in tumour than in normal gastric tissue. High tumour expression was associated with worse patient survival. Insulin receptor was detected readily in metastatic gastric adenocarcinoma cells and cell lines. Isoforms B and A were expressed. Pharmacological inhibition prevented cell growth and division, and induced caspase-dependent cell death. Rare tumour INS expression indicated tumours would be responsive to pancreatic or therapeutic insulins. Insulin stimulated gastric adenocarcinoma cell PI3-kinase/Akt signal transduction, proliferation, and survival. Insulin receptor knockdown inhibited proliferation and induced programmed cell death. Type I IGF receptor knockdown did not induce cell death. Conclusions The insulin and IGF signal transduction pathway is dominant in gastric adenocarcinoma. Gastric adenocarcinoma cell survival depends upon insulin receptor. That insulin has direct cancer-promoting effects on tumour cells has implications for clinical management of obese and diabetic cancer patients.

2021 ◽  
Vol 22 (5) ◽  
Jie Wang ◽  
Jingyun Zha ◽  
Xiaolin Wang

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Alif Aiman Zakaria ◽  
Mohd Hezmee Mohd Noor ◽  
Hafandi Ahmad ◽  
Hasliza Abu Hassim ◽  
Mazlina Mazlan ◽  

The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, β-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.

2021 ◽  
pp. 1-7
Mohamed A. A. Orabi ◽  
Sabry A. H. Zidan ◽  
Hiroshi Sakagami ◽  
Yukio Murakami ◽  
Ashraf A. Ali ◽  

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1402
Elisa Baldelli ◽  
Emna El Gazzah ◽  
John Conor Moran ◽  
Kimberley A. Hodge ◽  
Zarko Manojlovic ◽  

KRAS mutations are one of the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and in lung adenocarcinomas in particular. Development of therapeutics targeting KRAS has been incredibly challenging, prompting indirect inhibition of downstream targets such as MEK and ERK. Such inhibitors, unfortunately, come with limited clinical efficacy, and therefore the demand for developing novel therapeutic strategies remains an urgent need for these patients. Exploring the influence of wild-type (WT) KRAS on druggable targets can uncover new vulnerabilities for the treatment of KRAS mutant lung adenocarcinomas. Using commercially available KRAS mutant lung adenocarcinoma cell lines, we explored the influence of WT KRAS on signaling networks and druggable targets. Expression and/or activation of 183 signaling proteins, most of which are targets of FDA-approved drugs, were captured by reverse-phase protein microarray (RPPA). Selected findings were validated on a cohort of 23 surgical biospecimens using the RPPA. Kinase-driven signatures associated with the presence of the KRAS WT allele were detected along the MAPK and AKT/mTOR signaling pathway and alterations of cell cycle regulators. FoxM1 emerged as a potential vulnerability of tumors retaining the KRAS WT allele both in cell lines and in the clinical samples. Our findings suggest that loss of WT KRAS impacts on signaling events and druggable targets in KRAS mutant lung adenocarcinomas.

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