Cytotoxicity, DNA binding and cell apoptosis induction of a zinc(ii) complex of HBrQ

MedChemComm ◽  
2015 ◽  
Vol 6 (12) ◽  
pp. 2224-2231 ◽  
Author(s):  
Hai-Rong Zhang ◽  
Yan-Cheng Liu ◽  
Ting Meng ◽  
Qi-Pin Qin ◽  
Shang-Feng Tang ◽  
...  
Keyword(s):  
Dna Binding ◽  
Antitumor Activity ◽  
Cell Apoptosis ◽  
Antitumor Effect ◽  
Apoptosis Induction ◽  
Mitochondria Dysfunction ◽  
Phase Arrest ◽  
Caspase Cascade

A zinc(ii) complex of HBrQ showed higher in vitro antitumor activity. It induced cell apoptosis in BEL-7404 cells via G2 phase arrest, led to mitochondria dysfunction and activation of caspase cascade. The central zinc(ii) should play a key role to enhance the antitumor effect

scholarly journals Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

2018 ◽  
Vol 19 (10) ◽  
pp. 3179 ◽  
Author(s):  
Hongling Gu ◽  
Na Li ◽  
Jiangkun Dai ◽  
Yaxi Xi ◽  
Shijun Wang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Apoptosis ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Dna Binding Affinity ◽  
Dose Dependent ◽  
Mcf 7

A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C3 position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.

scholarly journals Anlotininb as a Promising Inhibitor on Tumor Growth of Oral Squamous Cell Carcinoma Through Cell Apoptosis and Mitotic Catastrophe

2020 ◽  
Author(s):  
Zhaoming Deng ◽  
Wei Liao ◽  
Wei Wei ◽  
Guihua Zhong ◽  
Chao He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Growth Factor ◽  
Oral Cancer ◽  
Cell Apoptosis ◽  
Antitumor Effect ◽  
Growth Factor Receptor ◽  
Gene Expression Omnibus ◽  
Mitotic Catastrophe

Abstract BackgroundOral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. ResultsHigher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p<0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. ConclusionAnlotinib could exert an antitumor effect on oral cancer cells lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.

In Vitro Antitumor Activity of Newly Synthesized Pyridazin-3(2H)-One Derivatives via Apoptosis Induction

2018 ◽  
Vol 51 (10) ◽  
pp. 893-901 ◽  
Author(s):  
Najat Bouchmaa ◽  
Mounir Tilaoui ◽  
Youness Boukharsa ◽  
Abdessalam Jaâfari ◽  
Hassan Aît Mouse ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Apoptosis Induction

scholarly journals Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jai-Sing Yang ◽  
Chia-Chun Wu ◽  
Chao-Lin Kuo ◽  
Yu-Hsuan Lan ◽  
Chin-Chung Yeh ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Molecular Mechanisms ◽  
Fas Ligand ◽  
Leukemia Cells ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Apoptotic Pathways ◽  
Murine Leukemia

We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedG0/G1phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨm). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedG0/G1phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

scholarly journals Antitumor activity of a fungal glucan tylopilan and Propionibacterium acnes preparation

2014 ◽  
Vol 63 (3-4) ◽  
pp. 293-298 ◽  
Author(s):  
Jan Grzybek ◽  
Izabella Zgórniak-Nowosielska ◽  
Andrzej Kasprowicz ◽  
Barbara Zawilińska ◽  
Stanisław Kohlmunzer
Keyword(s):  
Immune Response ◽  
Antitumor Activity ◽  
Antitumor Effect ◽  
Propionibacterium Acnes ◽  
Single Injection ◽  
Fruiting Bodies ◽  
Mean Survival Time ◽  
Tumor Bearing ◽  
Cell Inoculation

The study evaluated the antitumor activity of tylopilan, aβ- (1→3) (1→6) linked glucan isolated from fruiting bodies of <i>Tylopilus felleus</i> (Bull.: Fr.) P. Karst. (<i>Boletaceae</i>), and <i>Propionibacterium acnes</i> (<i>P.a.</i>) preparation. The antitumor effect of tylopilan and <i>P.a.</i> used alone or in combination was studied in NMRI mice inoculated i.p. with 106 180-TG Crocker tumor cells. All experiments were based on a pretreatment with tylopilan and/or <i>P.a.</i> 5 days and/or 2 h before tumor cell inoculation. Mean survival time (MST) of tumor - bearing mice was significantly prolonged in comparison to control mice by a single injection of tylopilan (25 µg/mouse or 50 µg/mouse) or <i>P.a.</i> (1 mg/mouse). MST was 23.6; 22.8 days in the tylopilan injected mice and 17.5 in the control animals. Tylopilan injected in conjunction with <i>P.a.</i> prolonged signifi-cantly MST in comparison to control mice as well as to tylopilan alone treated mice. We have found that <i>P.a.</i> which stimulate immune response enhanced significantly antitumor activity of tylopilan. The cytotoxicity of tylopilan at concentrations of 300, 150, 75 and 37.5 µg/ml towards 180-TG Crocker cells in vitro studies was evaluated. All examined tylopilan concentrations showed cytotoxic activity.

scholarly journals The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma

2018 ◽  
Vol 2 (23) ◽  
pp. 3516-3525 ◽  
Author(s):  
Kyle Runckel ◽  
Matthew J. Barth ◽  
Cory Mavis ◽  
Juan J. Gu ◽  
Francisco J. Hernandez-Ilizaliturri
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Effect ◽  
Ex Vivo ◽  
B Cell Lymphoma ◽  
Sensitive Cell ◽  
In Vivo Models ◽  
Synergistic Enhancement

Abstract Clinical observations suggest the existence of shared resistance pathways between rituximab and chemotherapy agents. To explore the mechanisms of rituximab resistance, our group created rituximab-resistant cell lines (RRCLs), which display altered expression of several inhibitor of apoptosis (IAP) family proteins. Here, we provide evidence to support pharmacologically targeting IAPs in lymphoma with LCL-161, a small molecule mimetic of the second mitochondria-derived activator of caspases (SMAC). The antitumor effect of LCL-161 was determined using luminescent adenosine triphosphate assays, flow cytometry, SCID mouse xenografts, and ex vivo patient biopsy sample studies. In vitro exposure to LCL-161 also resulted in a dose-dependent decrease in IAP levels, along with synergistic enhancement of the antitumor effect of cytotoxic chemotherapy, in rituximab-sensitive cell lines and RRCLs. In addition, LCL-161 increased the cytotoxic effect of the proteasome inhibitor carfilzomib in ex vivo lymphoma patient samples. The combination of LCL-161 with the chemotherapy regimen rituximab, gemcitabine, and vinorelbine (RGV) improved in vivo survival compared with RGV alone in severe combined immunodeficient mice implanted with RRCLs but not in animals implanted with rituximab-sensitive cell lines. In summary, LCL-161 exhibits synergistic antitumor activity in both in vitro and in vivo models of resistant lymphoma. Our data support further preclinical investigation of LCL-161 as a novel antilymphoma agent.

scholarly journals Romidepsin Induces G2/M Phase Arrest and Apoptosis in Cholangiocarcinoma Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382096075
Author(s):  
Pihong Li ◽  
Luguang Liu ◽  
Xiangguo Dang ◽  
Xingsong Tian
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Antitumor Effect ◽  
Caspase 3 ◽  
M Cell ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
M Phase

Background: Cholangiocarcinoma (CCA) is an extremely intractable malignancy since most patients are already in an advanced stage when firstly discovered. CCA needs more effective treatment, especially for advanced cases. Our study aimed to evaluate the effect of romidepsin on CCA cells in vitro and in vivo and explore the underlying mechanisms. Methods: The antitumor effect was determined by cell viability, cell cycle and apoptosis assays. A CCK-8 assay was performed to measure the cytotoxicity of romidepsin on CCA cells, and flow cytometry was used to evaluate the effects of romidepsin on the cell cycle and apoptosis. Moreover, the in vivo effects of romidepsin were measured in a CCA xenograft model. Results: Romidepsin could reduce the viability of CCA cells and induce G2/M cell cycle arrest and apoptosis, indicating that romidepsin has a significant antitumor effect on CCA cells in vitro. Mechanistically, the antitumor effect of romidepsin on the CCA cell lines was mediated by the induction of G2/M cell cycle arrest and promotion of cell apoptosis. The G2/M phase arrest of the CCA cells was associated with the downregulation of cyclinB and upregulation of the p-cdc2 protein, resulting in cell cycle arrest. The apoptosis of the CCA cells induced by romidepsin was attributed to the activation of caspase-3. Furthermore, romidepsin significantly inhibited the growth of the tumor volume of the CCLP-1 xenograft, indicating that romidepsin significantly inhibited the proliferation of CCA cells in vivo. Conclusions: Romidepsin suppressed the proliferation of CCA cells by inducing cell cycle arrest through cdc2/cyclinB and cell apoptosis by targeting caspase-3/PARP both in vitro and in vivo, indicating that romidepsin is a potential therapeutic agent for CCA.

Sign in / Sign up

Export Citation Format

Share Document