scholarly journals Regulation of MAPKs Signaling Contributes to the Growth Inhibition of 1,7-Dihydroxy-3,4-dimethoxyxanthone on Multidrug Resistance A549/Taxol Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Zuo ◽  
Hui Jiang ◽  
Yan-Hong Zhu ◽  
Ya-Qin Wang ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multidrug Resistance ◽  
Western Blot ◽  
Cell Cycle Arrest ◽  
Nsclc Cell Line ◽  
Potent Inducer ◽  
Cell Lung Carcinoma ◽  
Cycle Arrest ◽  
Growth Inhibitory ◽  
Securidaca Inappendiculata

1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is a bioactive compound isolated fromSecuridaca inappendiculataHassk. and validated with antiproliferative activities on a panel of cancer cell lines. This study was designed to investigate its growth inhibitory effects on multidrug resistance (MDR) non-small cell lung carcinoma (NSCLC) cell line A549/Taxol and explore the possible linkage between modulation of MAPKs and the bioactivities. Its growth inhibitory potency on the cells was estimated by MTT assay, and flow cytometric analysis was employed to investigate its potential cell cycle arrest and proapoptosis effects. Expressions of hallmark proteins were assessed by Western-Blot method. The results showed A549/Taxol cells were sensitive to XAN. XAN inhibited the proliferation of A549/Taxol cells in the time and concentration dependent manners. It acted as a potent inducer of apoptosis and cell cycle arrest in the cells. Western-Blot investigation validated the proapoptosis and cell cycle arrest activities of XAN and the potential of MDR reversion. Upregulation of p38 by XAN, which accounted for the cell cycle arrest at G2 phase, and the downregulation of ERK associated with the proapoptosis activity were also revealed. Further analysis found p53 may be the central role mediated the bioactivities of MAPKs in A549/Taxol cells. Based on these evidences, a conclusion has been deduced that XAN could be a potential agent for MDR NSCLC therapy targeting specifically MAPKs.

scholarly journals Alantolactone pyrazoline analogue inhibits cancer cell proliferation and induces apoptosis in non-small cell lung carcinoma cells

2015 ◽  
Vol 10 (2) ◽  
pp. 409 ◽  
Author(s):  
Jing Lv ◽  
Ming-Qin Cao ◽  
Jian-Chun Yu
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Cycle Arrest ◽  
Chromatin Condensation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cycle Arrest ◽  
H460 Cells ◽  
Dose Dependent

<p>The aim of the current study was to evaluate the anticancer and apoptotic effects of alantolactone pyrazoline analogue in human non-small cell lung cancer (NCI-H460) cells. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide) assay was used to evaluate the cell viability while as fluorescence microscopy was used to assess the effect on apoptosis, cellular and nuclear morphology. Flow cytometry evaluated the effect of APA on cell cycle arrest in these cells. The results revealed that APA induced potent, time and dose-dependent cytotoxic effects on the growth of NCI-H460 cells. It also inhibited colony forming tendency as well as cell invasion capability of these cancer cells. APA induced dose-dependent nuclear and cellular morphological effects including chromatin condensation and DNA fragmentation. Flow cytometry revealed that the anticancer effects of APA might be due to its cell cycle arrest inducing tendency in G0/G1 phase of the cell cycle.</p>

scholarly journals Antiproliferative and Apoptosis-Inducing Activities of Benchalokawichian Remedy Against Doxorubicin-Sensitive and -Resistant Erythromyelogenous Leukemic Cells

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Wipob Suttana ◽  
Chatubhong Singharachai ◽  
Rawiwan Charoensup ◽  
Narawadee Rujanapun ◽  
Chutima Suya
Keyword(s):  
Cell Cycle ◽  
Multidrug Resistance ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Drug Resistant ◽  
Normal Cells ◽  
Root Extracts ◽  
Cycle Arrest

Chemotherapy can cause multidrug resistance in cancer cells and is cytotoxic to normal cells. Discovering natural bioactive compounds that are not cytotoxic to normal cells but inhibit proliferation and induce apoptosis in drug- sensitive and drug-resistant cancer cells could overcome these drawbacks of chemotherapy. This study investigated the antiproliferative effects of crude extracts of Benchalokawichian (BLW) remedy and its herbal components against drug-sensitive and drug-resistant cancer cells, cytotoxicity of the extracts toward normal cells, and their ability to induce apoptosis and cell cycle arrest in drug-sensitive and drug-resistant cancer cells. The extracts exhibited antiproliferative activity against doxorubicin-sensitive and doxorubicin-resistant erythromyelogenous leukemic cells (K562 and K562/adr). Tiliacora triandra root, BLW, and Harrisonia perforata root extracts displayed an IC50 of 77.00 ± 1.30, 79.33 ± 1.33, and 87.67 ± 0.67 µg/mL, respectively, against K562 cells. In contrast, Clerodendrum petasites, T. triandra, and H. perforata root extracts displayed the lowest IC50 against K562/adr cells (68.89 ± 0.75, 78.33 ± 0.69, and 86.78 ± 1.92 µg/mL, respectively). The resistance factor of the extracts was lower than that of doxorubicin, indicating that the extracts could overcome the multidrug resistance of cancer cells. Importantly, the extracts were negligibly cytotoxic to peripheral mononuclear cells, indicating minimal adverse effects in normal cells. In addition, these extracts induced apoptosis of K562 and K562/adr cells and caused cell cycle arrest at the G0/G1 phase in K562 cells. Keywords: Antiproliferative, Apoptosis, Benchalokawichian, Cell cycle, Multidrug resistance

scholarly journals Photoinduced ROS regulation of apoptosis and mechanism studies of iridium(iii) complex against SGC-7901 cells

RSC Advances ◽  
2017 ◽  
Vol 7 (29) ◽  
pp. 17752-17762 ◽  
Author(s):  
Cheng Zhang ◽  
Shang-Hai Lai ◽  
Hui-Hui Yang ◽  
De-Gang Xing ◽  
Chuan-Chuan Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Cell Invasion ◽  
Cycle Arrest

A new iridium(iii) complex, Ir(ppy)2(FBPIP)]PF6 (Ir-1), was synthesized and characterized. The anticancer activity of the complex was investigated by cytotoxicity in vitro, apoptosis, cell invasion, autophagy, cell cycle arrest and western blot.

scholarly journals Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 572 ◽  
Author(s):  
Shi-qi Lin ◽  
Fu-juan Jia ◽  
Cai-yun Zhang ◽  
Fang-yuan Liu ◽  
Jia-hui Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cycle Arrest ◽  
M Phase

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins’ expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

Nutlin-3A, an MDM2 Antagonist, Induces p53-Dependent Cell Cycle Arrest and Apoptosis in Hodgkin Lymphoma (HL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2506-2506
Author(s):  
Elias Drakos ◽  
Athanasios Thomaides ◽  
Jiang Li ◽  
Marina Konopleva ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Western Blot ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
P53 Gene ◽  
Cycle Arrest

Abstract p53 is the most frequently mutated tumor suppressor gene in human cancer. However, in Hodgkin lymphoma (HL) p53 is mutated only in a small subset of cases suggesting that modulation of wild-type-p53 (wt-p53) levels in Hodgkin and Reed-Sternberg (HRS) cells may have therapeutic implications in these patients. MDM2 (HDM2 in humans) is a physiologic negative regulator of p53 levels through a well-established auto-regulatory feedback loop. Nutlin-3A is a recently developed small molecule, which antagonizes mdm2 through disruption of p53-MDM2 interaction resulting in p53 stabilization. We hypothesized that nutlin 3A may stabilize p53 in HRS cells carrying wt-p53 gene, thus leading to p53-dependent apoptosis and G1-S cell cycle arrest. We used two novel classical HL cell lines recently established in our Institution, MDA-V and MDA-E, which have been shown to carry wt-p53 gene. As a control, we used a HL cell line L-428 harboring a mutant p53 (mt-p53) gene product (deletion at exon 4). We investigated effects on apoptosis and cell cycle arrest after treatment of cultured HRS cells with nutlin-3A or a 150-fold less active enantiomere, nutlin-3B. Treatment with nutlin-3A resulted in substantial cell death (up to 65%) in a concentration-dependent manner associated with increased apoptosis as shown by apoptotic morphology (DAPI immunofluorescence), annexin V binding (flow cytometry) and caspase activation (Western blot analysis) in MDA-V and MDA-E cells, but not in L-428 cells. Nutlin-3A-induced apoptotic cell death was accompanied by stabilization of p53 protein as detected by western blot analysis and immunofluorescence and up-regulation of pro-apoptotic Bax, a known target of p53. Inhibition of nuclear export by leptomycin B stabilized p53 at a similar level as compared to nutlin-3A treatment in these cells, suggesting that nutlin-3A stabilized p53 through inhibition of MDM2-mediated degradation of the protein. By contrast, no changes in cell viability, growth or apoptosis were seen after treatment with the inactive nutlin-3B small molecule. Treatment with nutlin-3A also resulted in a significant decrease (up to 85%) of cells in S-phase and a dose-dependent increase of cells in G1 phase of cell cycle as detected by flow cytometry, in MDA-V and MDA-E cells, but not in L-428 cells. Cell cycle arrest was associated with up-regulation of the cyclin-dependent kinase inhibitor p21, a transcriptional target of p53. In contrast, treatment of HRS cells with nutlin-3B had no effects on the cell cycle irrespective of p53 mutation status. Furthermore, combined treatment with nutlin-3A and doxorubicin revealed synergistic effects and enhanced cytotoxicity in HRS cells with wt-p53 gene. Targeting MDM2 with the specific antagonist nutlin-3A that leads to non-genotoxic p53 activation, apoptosis induction and cell cycle inhibition may provide a new therapeutic approach for patients with HL.

scholarly journals NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Vanessa Andries ◽  
Karl Vandepoele ◽  
Katrien Staes ◽  
Geert Berx ◽  
Pieter Bogaert ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Inhibitory Effects ◽  
Cycle Arrest ◽  
Growth Inhibitory ◽  
G1 Cell Cycle Arrest

Phosphorylation-deficient Stat1 inhibits retinoic acid–induced differentiation and cell cycle arrest in U-937 monoblasts

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2870-2878
Author(s):  
Anna Dimberg ◽  
Kenneth Nilsson ◽  
Fredrik Öberg
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
Cell Cycle Arrest ◽  
Nuclear Translocation ◽  
Ectopic Expression ◽  
Leukemic Cell ◽  
Potent Inducer ◽  
Cycle Arrest

All-trans retinoic acid (ATRA) is a potent inducer of terminal differentiation of immature leukemic cell lines in vitro and of acute promyelocytic leukemia (APL) cells in vivo. Recent reports have shown that ATRA induces the expression of several interferon-regulated genes, including signal transducer and activator of transcription (Stat)1. To investigate the role of Stat1 activation in ATRA signaling, sublines were established for the human monoblastic cell line U-937 constitutively expressing wild-type or phosphorylation-defective Stat1, mutated in the conserved tyrosine 701 required for dimerization and nuclear translocation. Results showed that ATRA induction leads to activation of Stat1 by the phosphorylation of tyrosine 701 and subsequent nuclear translocation. Consistent with a functional importance of this activation, ectopic expression of Stat1Y701F suppressed ATRA-induced morphologic differentiation and expression of the monocytic surface markers CD11c and the granulocyte colony-stimulating factor receptor. Moreover, ATRA-induced growth arrest in the G0/G1phase of the cell cycle was inhibited by phosphorylation-deficient Stat1. Taken together, these results indicate that Stat1 is a key mediator of ATRA-induced cell cycle arrest and differentiation of U-937 cells.

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