scholarly journals Screening of Hibiscus and Cinnamomum Plants and Identification of Major Phytometabolites in Potential Plant Extracts Responsible for Apoptosis Induction in Skin Melanoma and Lung Adenocarcinoma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Neha Kaushik ◽  
Hyunji Oh ◽  
Yeasol Lim ◽  
Nagendra Kumar Kaushik ◽  
Linh Nhat Nguyen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Plant Extracts ◽  
A549 Cells ◽  
Skin Melanoma ◽  
Plant Parts ◽  
Cancer Cell Death ◽  
Clinical Drug Development ◽  
Targeting Delivery ◽  
Site Targeting ◽  
Ethanol Extracts

Carcinogenesis is a major concern that severely affects the human population. Owing to persistent demand for novel therapies to treat and prohibit this lethal disease, research interest among scientists is drawing its huge focus toward natural products, as they have minimum toxicity comparable with existing treatment methods. The plants produce secondary metabolites, which are known to have the anticancer potential for clinical drug development. Furthermore, the use of nanocarriers could boost the solubility and stability of phytocompounds to obtain site-targeting delivery. The identification of potential phytochemicals in natural compounds would be beneficial for the synthesis of biocompatible nanoemulsions. The present study aimed to investigate the potential cytotoxicity of ethanol extracts of Hibiscus syriacus and Cinnamomum loureirii Nees plant parts on human skin melanoma (G361) and lung adenocarcinoma (A549) cells. Importantly, biochemical analysis results showed the presence of high phenol (50–55 µgGAE/mg) and flavonoids [42–45 µg quercetin equivalents (QE)/mg] contents with good antioxidant activity (40–58%) in C. loureirii Nees plants extracts. This plant possesses potent antiproliferative activity (60–90%) on the malignant G361 and A549 and cell lines correlated with the production of nitric oxide. Especially, C. loureirii plant extracts have major metabolites that exhibit cancer cell death associated with cell cycle arrest. These findings support the potential application of Cinnamomum for the development of therapeutic nanoemulsion in future cancer therapy.

scholarly journals Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yuqing Lou ◽  
Jianlin Xu ◽  
Yanwei Zhang ◽  
Wei Zhang ◽  
Xueyan Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Quantitative Polymerase Chain Reaction ◽  
Mutant Cell ◽  
A549 Cells ◽  
The Cancer Genome Atlas ◽  
Akt Kinase ◽  
Egfr Expression

AbstractEpidermal growth factor receptor (EGFR) is a key oncogene in lung adenocarcinoma (LUAD). Resistance to EGFR tyrosine kinase inhibitors is a major obstacle for EGFR-mutant LUAD patients. Our gene chip array, quantitative polymerase chain reaction validation, and shRNA-based high-content screening identified the Akt kinase lanthionine synthetase C-like protein 2 (LANCL2) as a pro-proliferative gene in the EGFR-mutant LUAD cell line PC9. Therefore, we investigated whether LANCL2 plays a role in promoting cell proliferation and drug resistance in EGFR-mutant LUAD. In silico clinical correlation analysis using the Cancer Genome Atlas Lung Adenocarcinoma dataset revealed a positive correlation between LANCL2 and EGFR expression and an inverse relationship between LANCL2 gain-of-function and survival in LUAD patients. The EGFR-mutant LUAD cell lines PC9 and HCC827 displayed higher LANCL2 expression than the non-EGFR-mutant cell line A549. In addition, LANCL2 was downregulated following gefitinib+pemetrexed combination therapy in PC9 cells. LANCL2 knockdown reduced proliferation and enhanced apoptosis in PC9, HCC827, and A549 cells in vitro and suppressed murine PC9 xenograft tumor growth in vivo. Notably, LANCL2 overexpression rescued these effects and promoted gefitinib + pemetrexed resistance in PC9 and HCC827 cells. Pathway analysis and co-immunoprecipitation followed by mass spectrometry of differentially-expressed genes in LANCL2 knockdown cells revealed enrichment of several cancer signaling pathways. In addition, Filamin A and glutathione S-transferase Mu 3 were identified as two novel protein interactors of LANCL2. In conclusion, LANCL2 promotes tumorigenic proliferation, suppresses apoptosis, and promotes gefitinib+pemetrexed resistance in EGFR-mutant LUAD cells. Based on the positive association between LANCL2, EGFR, and downstream Akt signaling, LANCL2 may be a promising new therapeutic target for EGFR-mutant LUAD.

scholarly journals Radio-sensitization effect of an mTOR inhibitor, temsirolimus, on lung adenocarcinoma A549 cells under normoxic and hypoxic conditions

2015 ◽  
Vol 56 (4) ◽  
pp. 663-668 ◽  
Author(s):  
Hiroki Ushijima ◽  
Yoshiyuki Suzuki ◽  
Takahiro Oike ◽  
Mayumi Komachi ◽  
Yuya Yoshimoto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mtor Inhibitor ◽  
A549 Cells ◽  
Hypoxic Conditions ◽  
Lung Adenocarcinoma A549 ◽  
Sensitization Effect

Dual Enzyme-Like Performances of PLGA Grafted Maghemite Nanocrystals and Their Synergistic Chemo/Chemodynamic Treatment for Human Lung Adenocarcinoma A549 Cells

2021 ◽  
Vol 17 (6) ◽  
pp. 1007-1019
Author(s):  
Miao Cui ◽  
Hui-Ru Zhang ◽  
Fan Ouyang ◽  
Yu-Qi Guo ◽  
Rui-Fang Li ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Lung Adenocarcinoma ◽  
Therapeutic Strategy ◽  
A549 Cells ◽  
Inorganic Nanoparticles ◽  
Poly Lactic Acid ◽  
Dual Response ◽  
Catalytically Active ◽  
Endogenous Peroxidase ◽  
Lung Adenocarcinoma A549

In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles with dual response of endogenous peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe2O3 nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe2O3 nanoparticles could simulate the activity of catalase and decompose hydrogen peroxide into H2O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe2O3 nanoparticles could simulate the activity of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe2O3 nanoparticles and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe2O3 nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic nanozymes for the treatment of lung cancer.

scholarly journals Stimulation of phenolic compounds production in the in vitro cultivated Polyscias filicifolia Bailey shoots and evaluation of the antioxidant and cytotoxic potential of plant extracts

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Anita Agnieszka Śliwińska ◽  
Katarzyna Sykłowska-Baranek ◽  
Anita Kośmider ◽  
Sebastian Granica ◽  
Karolina Miszczak ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Antioxidant Capacity ◽  
Cytotoxic Activity ◽  
Phenolic Compound ◽  
Plant Extracts ◽  
Detrimental Effect ◽  
A549 Cells ◽  
Ferulic Acids

<p>In this study, an efficient method to enhance phenolic compound production in the in vitro cultured shoots of <em>Polyscias filicifolia</em> was developed. The phenolic compound content in <em>P. filicifolia</em> has not yet been reported. Shoots were treated with methyl jasmonate (JM) or salicylic acid (SA) at doses of 50, 100, or 200 µM. HPLC-UV-VIS and LC-MS techniques were used for the determination of chlorogenic, caffeic, and ferulic acids. The total phenolics and flavonoids were quantified, and the antioxidant capacity of plant extracts was determined using DPPH and ABTS methods. Finally, the cytotoxic activity of <em>P. filicifolia</em> extracts in normal (HaCaT) and cancer (A549) cells was investigated. Further, the effect of the extracts on cisplatin cytotoxicity was assessed.</p><p>The elicitors significantly enhanced phenolic production compared to that in untreated shoots and leaves of intact plants. Chlorogenic acid was the most abundant compound with the highest yield of 5.03 ±0.25 mg/g DW after treatment with 50 µM SA. The total flavonoid and phenolic content was significantly and dose-dependently influenced by JM. The highest antioxidant capacity was noted in extracts derived from shoots grown on media supplemented with 50 µM SA and 200 µM JM; these doses were used for further cytotoxic activity investigations. The extracts from JM or SA treatments reduced cancer cell viability and increased their mortality, whereas the extract from JM treatment exhibited protective effect on normal cells. Moreover, the comparison of cytotoxic properties of plant extracts and cisplatin indicated that plant phenolic compounds in combination with anticancer drugs could reduce the detrimental effect of the latter on human cells.</p>

scholarly journals Increased STIP1 and Hsp90 Correlate with Progression and Prognosis of Lung Adenocarcinoma

2021 ◽  
Author(s):  
Biaoxue Rong ◽  
Youwen Zhang ◽  
Junye Wang ◽  
Shucheng Ye ◽  
Maoqing Guo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Malignant Tumors ◽  
Clinical Stage ◽  
A549 Cells ◽  
Biological Behavior ◽  
Prognostic Indicators ◽  
Normal Lung ◽  
Clinicopathological Parameters ◽  
Strong Positive Correlation ◽  
Advanced Clinical Stage

Abstract Background: Stress-inducible phosphoprotein 1 (STIP1) and heat shock protein 90 (Hsp90) have been found to be correlated with malignant tumors. The aim of this investigation was to study the relationship between their expressions and lung adenocarcinoma (LAC). Methods: The expressions of STIP1and Hsp90 in LAC cells and tissues were tested by immunohistochemistry and western blot; the correlation between their expressions and clinicopathological parameters of LAC was analyzed by survival analysisand multiple regression analysis. Results: Expressions of STIP1 and Hsp90 were higher in A549 cells and LAC tissues than that in 16 human bronchial epithelial cells (16HBE cells) (P<0.05) and adjacent normal lung tissues (P < 0.05). The expression of STIP1 and Hsp90 in LAC showed a strong positive correlation (P < 0.05) and significantly correlated with lymph node metastasis (P < 0.05), advanced clinical stage (P < 0.05) and shorter survival (P < 0.05) of LAC. Conclusions: Increased expressions of STIP1 and Hsp90 were closely related to malignant biological behavior of LAC, suggesting that they could be used as potential biomarkers and prognostic indicators for LAC.

scholarly journals p62 Overexpression Promotes Bone Metastasis of Lung Adenocarcinoma out of LC3-Dependent Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Dongqi Li ◽  
Chuanchun He ◽  
Fan Ye ◽  
En Ye ◽  
Hao He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Survival Rates ◽  
A549 Cells ◽  
Adaptor Protein ◽  
Beclin 1 ◽  
Cox Regression Analysis

p62 protein has been implicated in bone metastasis and is a multifunctional adaptor protein usually correlated with autophagy. Herein, we investigated p62 expression and its prognostic significance in bone metastasis of lung adenocarcinoma, and analyzed whether the mechanism involved depends on autophagy. mRNA and protein expression of p62, LC3B and Beclin 1 were detected by reverse transcription-quantitative PCR and western blotting, respectively, in fresh bone metastasis tissues (n=6 cases) and normal cancellous bone tissues (n=3 cases). The association between p62 and LC3B expression and patient prognosis was subsequently analyzed in 62 paraffin-embedded bone metastasis specimens by immunohistochemistry assay. Small interfering RNA (siRNA) was employed to downregulate p62 expression in SPC-A-1 and A549 cells. Cell proliferation and migration ability were tested by CCK8, CCF and Transwell assays respectively. Autophagy was induced by Rapamycin or inhibited by Atg 7 knockout/Chloroquine in A549 cells and p62 and LC3II/I expression were analyzed. After subcutaneous inoculation or intracardial injection of A549 cells into nude mice, the effect of p62 downregulation in vivo was analyzed by histopathological examination. The results showed that p62, LC3B and Beclin 1 mRNA and protein were all overexpressed in bone metastasis tissues (all P&lt;0.01). Patient samples with high p62 expression levels were significantly associated with more bone lesions (&gt;3), shorter overall survival rates and shorter progression free survival rates compared with patients having lower p62 expression (P=0.014, P=0.003, P=0.048, respectively). Cox regression analysis identified p62 expression as an independent prognostic indicator of overall survival of patients with bone metastasis (P=0.007). In vitro p62 downregulation inhibited SPC-A-1 and A549 cells migration but had no effect on cell proliferation. After autophagy induction or inhibition, p62 expression involved in autophagy flux and changed inconsistently according to the switch of LC3I to LC3II in different autophagy conditions. In vivo p62 downregulation had no effect on growth of subcutaneous tumor. Lung or bone metastasis lesion was not found in all mice model. These findings suggested that p62 overexpression promotes tumor cell invasion out of LC3-dependent autophagy, which could be used a potential prognostic biomarker and therapeutic target for bone metastasis of lung adenocarcinoma.

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