Wedelia chinensisInhibits Nasopharyngeal Carcinoma CNE-1 Cell Growth by Inducing G2/M Arrest in a Chk1-Dependent Pathway

2013 ◽  
Vol 41 (05) ◽  
pp. 1153-1168 ◽  
Author(s):  
Manyu Liu ◽  
Weizhang Wang ◽  
Xiaobo Li ◽  
Dayu Shi ◽  
Hanfang Mei ◽  
...  
Keyword(s):  
Cell Growth ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Intervention Strategy ◽  
M Cell ◽  
Human Cancer Cell Lines

Although Wedelia chinensis, an herb in traditional Chinese medicine, has been widely used for the treatment of inflammation, the effects of W. chinensis on cancer cell growth and the related molecular mechanisms behind these effects have largely remained unexplored to date. In the present study, W. chinensis plant extracts were obtained using either ethanol (E), petroleum ether (PE), ethyl acetate (EA) or butyl alcohol (BA). Then, extracts were examined for bioactivity in vitro via MTT assay in five human cancer cell lines. Our results showed that one subfraction of the EA extract (EA6) was cytotoxic to nasopharyngeal carcinoma (NPC) CNE-1 cells, among all cell lines evaluated. Treatment of CNE-1 cells with EA6 resulted in significant G2/M cell cycle arrest and modest apoptosis. EA6 induced Chk1 activation and inhibition of Chk1 in CNE-1 cells by RNA interference (RNAi) markedly abrogated EA6-mediated G2/M arrest and abolished EA6-induced cytotoxicity. EA6 treatment resulted in notable reduction of c-myc expression in CNE-1 cells, whereas silencing Chk1 inhibited such effects of EA6. Our results indicate that Chk1 is a novel molecular target of EA6 in NPC cells and also suggest an intervention strategy for NPC by EA6 exploring its molecular mechanisms of action.

scholarly journals In Vitro Radiosensitization by Eribulin in Human Cancer Cell Lines

2021 ◽  
Author(s):  
Raquel Benlloch ◽  
Raquel Castejón ◽  
Silvia Rosado ◽  
María José Coronado ◽  
Patricia Sánchez ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Cancer Cell ◽  
Drug Exposure ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
M Cell ◽  
Human Cancer Cell Lines ◽  
Fadu Cells

Abstract Objectives: To determine the radiosensitizing properties of eribulin and to establish the potential mechanisms of radiosensitization in cervical (HeLa) and pharyngeal (FaDu) cancer cell lines.Material and Methods: Cytotoxicity was evaluated by the crystal violet method. The 10% and 50% inhibitory concentration (IC10, IC50) for 24-hour drug exposure were determined in both cell lines. The surviving fraction at 2Gy (SF2) and the sensitizer enhancement ratio (SER) were calculated from radiation cell survival curves in presence or absence of eribulin. Combination index (CI) was calculated to determine if there is a true synergistic interaction between eribulin and irradiation. Cell cycle changes were assessed by propidium iodide staining and flow cytometry analysis. Apoptotic cells were detected by FITC-conjugated annexin-V labelling and flow cytometry and by immunofluorescence with TUNEL-assay.Results: Mean IC50s and IC10s were 1.58nM and 0.7nM and 0.7nM and 0.27nM for HeLa and FaDu cells respectively. Radiosensitization was observed in both lines tested with a SER up to 2.71 and 2.32 for HeLa and FaDu cells respectively. A true synergistic effect was showed with a CI of 0.82 and 0.76 for HeLa and FaDu cells respectively. Eribulin induced significant G2/M cell arrest and marked apoptosis. Irradiation combined with 3nM eribulin enhanced radiation induced apoptosis in Hela cells.Conclusions: Eribulin shows a true in vitro radiosensitizing effect in tested cell lines by inducing significant G2/M phase arrest and apoptosis changes. Further studies are needed to assess the clinical benefits of concurrent eribulin and radiotherapy as a novel therapeutic strategy for cancer.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

scholarly journals Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3923
Author(s):  
Adel A.-H. Abdel-Rahman ◽  
Amira K. F. Shaban ◽  
Ibrahim F. Nassar ◽  
Dina S. EL-Kady ◽  
Nasser S. M. Ismail ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

scholarly journals SPIONs/3D SiSBA-16 based Multifunctional Nanoformulation for target specific cisplatin release in colon and cervical cancer cell lines

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
B. Rabindran Jermy ◽  
Munther Alomari ◽  
Vijaya Ravinayagam ◽  
Sarah Ameen Almofty ◽  
Sultan Akhtar ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Magnetic Resonance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Dapi Staining ◽  
Tem Analysis ◽  
Human Cancer Cell Lines

Abstract Multifunctional nanomaterials can be used for dual applications: drug delivery as well as in bioimaging. In current study, we investigated potential use of silica based supports; 3D cage type SiSBA-16 (S-16), monodispersed hydrophilic spherical silica (HYPS) and mesocellular foam (MSU-F) for cisplatin (Cp) delivery. To obtain magnetic resonance characteristics, 10 wt% iron oxide was loaded through enforced adsorption technique. For pH stimuli responsive release of Cp, 10 wt%SPIONs/S-16 was functionalized with 3-(Aminopropyl)triethoxysilane (A) and poly acrylic acid (PAA) termed as 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp. By TEM analysis, the average diameter of the SPIONs was found to range between 10–60 nm. VSM analysis showed saturation magnetization over S-16, HYPS and MSU-F were in the following order: 10 wt%SPIONs/HYPS (4.08 emug−1) > 10 wt%SPIONs /S-16 (2.39 emug−1) > 10 wt%SPIONs/MSU-F (0.23 emug−1). Cp release study using dialysis membrane in PBS solution over 10 wt%SPIONs/S-16 nanoformulations showed highest cumulative release (65%) than 10 wt%SPIONs/MSU-F-A-Cp (63%), 10 wt%SPIONs/HYPS-A-Cp (58%), and Cp-F127/S-16 (53%), respectively. 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp were evaluated for in vitro target anticancer efficiency in human cancer cell lines (colon cancer (HCT 116), cervical cancer (HeLa)) and normal cells (Human embryonic kidney cells (HEK293) using MTT and DAPI staining. 10 wt%SPIONs/S-16-A-Cp treated Hela and HCT116 cancerous cell lines showed significant control of cell growth, apoptotic activity and less cytotoxic effect as compared to Cp and 10 wt%SPIONs/S-16. Target specific Cp release in the cells shows that 10 wt%SPIONs/S-16-A-Cp can be easily upgraded for magnetic resonance imaging capability.

scholarly journals Fucoidan, a major component of brown seaweed, prohibits the growth of human cancer cell lines in vitro

2008 ◽  
Author(s):  
Suguru Fukahori ◽  
Hirohisa Yano ◽  
Jun Akiba ◽  
Sachiko Ogasawara ◽  
Seiya Momosaki ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Brown Seaweed ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines
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