Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers

Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers. After initial screening and further structure optimization, we identified Aa3 as a dose-dependent ANO1 blocker. This compound exhibited more potent anti-cancer activity in the NCI-H460 cell line, expressing high levels of ANO1 compared with that in A549 cells that express low levels of ANO1. Our results open a new direction for the development of small-molecule ANO1 blockers composed of a pyrimidine scaffold and a nitrogen-containing heterocyclic moiety, with drug-like properties.

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Evaluation of the anti-cancer potential of Cedrus deodara total lignans by inducing apoptosis of A549 cells

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2682-6 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Xiaofeng Shi ◽

Ruiqin Du ◽

Junmin Zhang ◽

Yanping Lei ◽

Hongyun Guo

Keyword(s):

Cell Cycle ◽

Therapeutic Potential ◽

Biological Activities ◽

A549 Cells ◽

Cedrus Deodara ◽

Anti Cancer ◽

M Phase ◽

Dose Dependent Fashion ◽

Dose Dependent ◽

Lung Adenocarcinoma Cancer

Abstract Background Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. Methods We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. Results The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 μg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. Conclusion At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.

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Anti-Cancer Activity of Catechin against A549 Lung Carcinoma Cells by Induction of Cyclin Kinase Inhibitor p21 and Suppression of Cyclin E1 and P–AKT

Applied Sciences ◽

10.3390/app10062065 ◽

2020 ◽

Vol 10 (6) ◽

pp. 2065

Author(s):

Haiyan Sun ◽

Meichen Yin ◽

Danqing Hao ◽

Yixiao Shen

Keyword(s):

Kinase Inhibitor ◽

A549 Cells ◽

Dependent Manner ◽

Cyclin E1 ◽

Lung Carcinoma Cells ◽

Cycle Arrest ◽

Anti Cancer ◽

Berry Fruits ◽

Dose Dependent ◽

Cancer Activity

Catechin is one of the major polyphenols in teas, beans, and berry fruits. A number of studies have confirmed that catechins extract possesses health benefits in the prevention of various chronic diseases. In this study, the anti-cancer activity and mechanism of catechin against non-small cell lung cancer A549 cells were investigated. The inhibitory rate of catechin on the proliferation of A549 cells reached 19.76% at a concentration of 600 μmol·L−1 with 24 h incubation. The results demonstrated that catechin inhibits A549 cells by increasing the expressions of p21 and p27 in the cancer cells. Furthermore, the catechin treatment inhibited the expressions of cyclin E1 and phosphorylation of protein kinase (P–AKT) in a dose-dependent manner, which also contributed to the inhibition of cancer cell proliferation. Therefore, the results of this study indicated that catechin can effectively inhibit the proliferation of A549 cells through regulating its cell cycle arrest or indirectly via the p21 signaling pathway. It would provide important information for developing catechin and catechin-rich functional food or co-therapy for antitumor purposes.

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Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200903121624 ◽

2020 ◽

Vol 21 ◽

Cited By ~ 1

Author(s):

Virginia Fuochi ◽

Massimo Caruso ◽

Rosalia Emma ◽

Aldo Stivala ◽

Riccardo Polosa ◽

...

Keyword(s):

Antibacterial Activity ◽

Bacterial Species ◽

A549 Cells ◽

Bactericidal Effect ◽

Minimal Bactericidal Concentration ◽

Viability Assay ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

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The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03204-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fatemeh Hosami ◽

Azadeh Manayi ◽

Vahid Salimi ◽

Farshad Khodakhah ◽

Mitra Nourbakhsh ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Caspase 3 ◽

Cannabis Sativa ◽

A549 Cells ◽

Echinacea Purpurea ◽

G1 Phase ◽

Cell Cycle Distribution ◽

Cb2 Receptor ◽

Anti Cancer

Abstract Background Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study. Methods The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit. Results Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells. Conclusions The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents. Graphical abstract

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Rare Chromone Derivatives from the Marine-Derived Penicillium citrinum with Anti-Cancer and Anti-Inflammatory Activities

Marine Drugs ◽

10.3390/md19010025 ◽

2021 ◽

Vol 19 (1) ◽

pp. 25

Author(s):

Yi-Cheng Chu ◽

Chun-Hao Chang ◽

Hsiang-Ruei Liao ◽

Ming-Jen Cheng ◽

Ming-Der Wu ◽

...

Keyword(s):

A549 Cells ◽

Penicillium Citrinum ◽

Signaling Cascades ◽

Human Neutrophils ◽

Cytotoxic Activities ◽

Western Blot Assay ◽

Chromone Derivatives ◽

Anti Cancer ◽

Ic50 Values ◽

Induced Apoptosis

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC50 values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC50 values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.

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