scholarly journals Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives

2021 ◽  
Vol 19 (1) ◽  
pp. 855-863
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Murad Abualhasan ◽  
Johnny Amer ◽  
Serkan Levent ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Positive Control ◽  
Cell Cycle Analysis ◽  
Anticancer Activities ◽  
Lipinski’S Rule ◽  
Value Range

Abstract The current study aimed to design and synthesize a novel series of fluorophenyl-isoxazole-carboxamide derivatives and evaluate their antiproliferative activities. Anticancer activities of the novel compounds were evaluated by MTS assay against four cancer cell lines, including liver (Hep3B, HepG2), cervical (HeLa), and breast (MCF-7), and α-fetoprotein tumor marker, cell cycle analysis, and annexin V tests. Chemo-informatics analysis showed that all synthesized derivatives 2a–2f obeyed Lipinski’s rule. Compound 2f was the most potent compound against Hep3B and Hep-G2 cancer cell lines with IC50 values of 5.76 and 34.64 µg/mL, respectively. Moreover, compounds 2a–2c and 2e showed potent inhibitory activity against Hep3B with an IC50 value range of 7.66–11.60 µg/mL. Hep3B secretions of α-fetoprotein (α-FP) results showed that compound 2f reduced the secretion of Hep3B to 168.33 ng/mL and compound 2d reduced the secretion to value approximately 598.33 ng/mL, in comparison with untreated cells’ value of 1116.67 ng/mL. Furthermore, cell cycle analysis showed that the 2f compound induced arrest in the G2-M phase in 6.73% of the total cells and that was lower than the activity of the positive control doxorubicin (7.4%). Moreover, 2b and 2f compounds reduced the necrosis rate of Hep3B to 4-folds and shifted the cells to apoptosis.

scholarly journals The cytotoxic and apoptotic effects of Ferulago W. Koch extracts on various cancer cell lines

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Filiz Bakar-Ates ◽  
Berna Hoti ◽  
Ilhan Gurbuz ◽  
Tugba Gunbatan ◽  
Hayri Duman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Antimicrobial Activities ◽  
Anticancer Activities ◽  
Ethanolic Extracts

AbstractBackgroundThe studies investigating the anticancer activities of natural products have accelerated to produce new solutions in the face of increasing cancer cases. Various Ferulago species are reported to exhibit antioxidant, antiulcer and antimicrobial activities.ObjectiveThis study aimed to evaluate the cytotoxic and apoptotic activities of ethanolic extracts of roots of five Ferulago species on various human cancer cell lines.Material and methodsHPLC analyses were performed by HP Agilent 1,100. The cytotoxicity were determined by MTT assay. The cell cycle arrest and Annexin V binding analyses were performed by Muse Cell Analyzer (Millipore).ResultsAll examined species except F. setifolia inhibited cell viability in PC3 and SW480 cells at 0.01 mg/mL and higher concentrations (p<0.05). Ferulago species inhibited cell cycle at different stages for treated cell lines. The ethanolic extracts of Ferulago species also increased Annexin V binding significantly, resulted in apoptosis (p<0.05%). In this context, F. syriaca showed the highest apoptotic activity in MCF-7 cells by increasing the apoptotic cell population to 23.54 ± 2.10% (p<0.0001).ConclusionThe findings of present study have shown that Ferulago species included in the study have potent anticancer effects and this work have the potential to result in further studies.

scholarly journals Design, Synthesis, In Vitro Anticancer Evaluation and Molecular Modelling Studies of 3,4,5-Trimethoxyphenyl-Based Derivatives as Dual EGFR/HDAC Hybrid Inhibitors

2021 ◽  
Vol 14 (11) ◽  
pp. 1177
Author(s):  
Tarek S. Ibrahim ◽  
Azizah M. Malebari ◽  
Mamdouh F. A. Mohamed
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Hydroxamic Acid ◽  
Phenyl Group ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Molecular Docking Study

Recently, combining histone deacetylase (HDAC) inhibitors with chemotherapeutic drugs or agents, in particular epidermal growth factor receptor (EGFR) inhibitors, is considered to be one of the most encouraging strategy to enhance the efficacy of the antineoplastic agents and decrease or avoid drug resistance. Therefore, in this work, based on introducing 3,4,5-trimethoxy phenyl group as a part of the CAP moiety, in addition to incorporating 4–6 aliphatic carbons linker and using COOH or hydroxamic acid as ZBG, 12 novel EGFR/HDAC hybrid inhibitors 2a–c, 3a–c, 4a–c and 5a–c were designed, constructed, and evaluated for their anticancer activities against 4 cancer cell lines (HepG2, MCF-7, HCT116 and A549). Among all, hybrids with hydroxamic acid 4a–c and 5a, exhibited the highest inhibition against all cancer cell lines with IC50 ranging from 0.536 to 4.892 μM compared to Vorinostat (SAHA) with IC50 ranging from 2.43 to 3.63 μM and Gefitinib with IC50 ranging from 1.439 to 3.366 μM. Mechanistically, the most potent hybrids 4a–c and 5a were further tested for their EGFR and HDACs inhibitory activities. The findings disclosed that hybrid 4b displayed IC50 = 0.063 µM on the target EGFR enzyme which is slightly less potent than the standard Staurosporine (IC50 = 0.044 µM). Furthermore, hybrid 4b showed less HDAC inhibitory activity IC50 against HDAC1 (0.148), 2 (0.168), 4 (5.852), 6 (0.06) and 8 (2.257) than SAHA. In addition, the investigation of apoptotic action of the most potent hybrid 4b showed a significant increase in Bax level up to 3.75-folds, with down-regulation in Bcl2 to 0.42-fold, compared to the control. Furthermore, hybrid 4b displayed an increase in the levels of Caspases 3 and 8 by 5.1 and 3.15 folds, respectively. Additionally, the cell cycle analysis of hybrid 4b revealed that it showed programmed cell death and cell cycle arrest at G1/S phase. Moreover, all these outcomes together with the molecular docking study recommended the rationalized target hybrids 4a–c and 5a, particularly 4b, may be considered to be promising lead candidates for discovery of novel anticancer agents via dual inhibition of both EGFR/HDAC enzymes.

scholarly journals Cytotoxic Activity of Cycloartane Triterpenoids from Sphaerophysa Salsula

2009 ◽  
Vol 4 (1) ◽  
pp. 1934578X0900400
Author(s):  
Dan Wang ◽  
Zhongjun Ma
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Western Blotting ◽  
Cancer Cell Lines ◽  
Cell Cycle Analysis ◽  
Cycloartane Triterpenoids ◽  
Sphaerophysa Salsula ◽  
Mcf 7

The cytotoxicity of three cycloartane triterpenoids, 9, 19-cycloart-7β, 24R, 25- triol-1-en-3-one (1), 9, 19-cycloart-7β, 24R, 25-triol-1-en-3-one 25-O-β-D-glucopynanoside (2), and 25-O-β-D-arabinopyranosyl-(1→4)- β-D-glucopyranosyl-9, 19-cycloart-7β, 24R, 25-triol-1-en-3-one (3), isolated from Sphaerophysa salsula was investigated on SF188, U87wt, MCF-7, and H460 cancer cell lines. Compound 1 showed the strongest activity. Cell cycle analysis was employed to elucidate the cytotoxicity on the tested U87wt cells, which led to G2/M arrest. In addition, from the Western blotting experiments, the expression of P21 is increased.

scholarly journals Berberine Induces Apoptosis and Arrests Cell Cycle in Multiple Cancer Cell lines

2021 ◽  
Author(s):  
Qian Li ◽  
Hui Zhao ◽  
Weimin Chen ◽  
Ping Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Multiple Cancer ◽  
Cycle Arrest ◽  
Ic50 Values ◽  
Mcf 7

IntroductionTo examine the anti-cancer effects of berberine on multiple cancer cell lines; and to clarify the underlying molecular mechanisms.Material and methodsThe IC50 values of berberine on Tca8113 (oral squamous cell carcinoma), CNE2 (nasopharyngeal carcinoma cell), MCF-7 (breast cancer), Hela (cervical carcinoma), and HT29 (colon cancer) cells were determined by MTT cell viability assay. Early apoptosis and cell cycle arrest was examined by flow cytometry with annexin V and propidium iodide (PI) staining, respectively. For expressions of BAX and BCL-2 genes and proteins were detected by real-time PCR and western blotting, respectively.ResultsBerberine displayed cytotoxic effect on all the cell lines tested. The IC50 values were determined (Tca8113, 218.52±18.71; CNE2, 249.18±18.14; MCF-7, 272.15±11.06; Hela, 245.18±17.33; and HT29, 52.37±3.45). PI staining revealed berberine treatment resulted in cell cycle arrest at G2/M. The treatment also induced early apoptosis as shown by annexin V staining. In addition, berberine significant elevated gene and protein expression of BAX, which was accompanied by substantial decreases in BCL-2 gene and protein levels. The effects of berberine on BAX and BCL-2 were time-dependent.ConclusionsBerberine exhibited cytotoxic effects on multiple cancer cell lines by inducing apoptosis and cell cycle arrest. The BCL-2/BAX signaling pathway may be the common pathway underlying the anti-tumor effect of berberine. The findings support the notion that berberine is a dietary compound that can be further developed into a drug candidate for cancer treatment.

scholarly journals Evaluation of the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 isolated from Lilium davidii var. unicolor (Hoog) Cotton

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Aiai Ma ◽  
Kan Jiang ◽  
Bin Chen ◽  
Shasha Chen ◽  
Xinge Qi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agent ◽  
Cancer Cell Lines ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Cycle Arrest ◽  
Lilium Davidii

Abstract Background Endophytic actinomycetes, as emerging sources of bioactive metabolites, have been paid great attention over the years. Recent reports demonstrated that endophytic streptomycetes could yield compounds with potent anticancer properties that may be developed as chemotherapeutic drugs. Results Here, a total of 15 actinomycete-like isolates were obtained from the root tissues of Lilium davidii var. unicolor (Hoog) Cotton based on their morphological appearance, mycelia coloration and diffusible pigments. The preliminary screening of antagonistic capabilities of the 15 isolates showed that isolate LRE541 displayed antimicrobial activities against all of the seven tested pathogenic microorganisms. Further in vitro cytotoxicity test of the LRE541 extract revealed that this isolate possesses potent anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cell lines RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1990, and A549, respectively. LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rRNA gene sequence analysis. It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. To further explore the mechanism underlying the decrease of cancer cell viability following the LRE541 extract treatment, cell apoptosis and cell cycle arrest assays were conducted in two cancer cell lines, RKO and 7901. The result demonstrated that LRE541 extract inhibited cell proliferation of RKO and 7901 by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose-dependent manner. The chemical profile of LRE541 extract performed by the UHPLC-MS/MS analysis revealed the presence of thirty-nine antitumor compounds in the extract. Further chemical investigation of the LRE541 extract led to the discovery of one prenylated indole diketopiperazine (DKP) alkaloid, elucidated as neoechinulin A, a known antitumor agent firstly detected in Streptomyces; two anthraquinones 4-deoxy-ε-pyrromycinone (1) and epsilon-pyrromycinone (2) both displaying anticancer activities against RKO, SW1990, A549, and HepG2 with IC50 values of 14.96 ± 2.6 − 20.42 ± 4.24 μg/mL for (1); 12.9 ± 2.13, 19.3 ± 4.32, 16.8 ± 0.75, and 18.6 ± 3.03 μg/mL for (2), respectively. Conclusion Our work evaluated the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 and obtained one prenylated indole diketopiperazine alkaloid and two anthraquinones. Neoechinulin A, as a known antitumor agent, was identified for the first time in Streptomyces. Though previously found in Streptomyces, epsilon-pyrromycinone and 4-deoxy-ε-pyrromycinone were firstly shown to possess anticancer activities. Graphical Abstract

Influence of AUF1 targeting siRNA on cell cycle-related proteins in thyroid cancer cell lines

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
B Trojanowicz ◽  
Z Chen ◽  
J Bialek ◽  
Y Radestock ◽  
S Hombach-Klonisch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines ◽  
Related Proteins
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