scholarly journals Polyphenol Extract from Evening Primrose (Oenothera paradoxa) Inhibits Invasion Properties of Human Malignant Pleural Mesothelioma Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1574
Author(s):  
Malgorzata Chmielewska-Kassassir ◽  
Katarzyna Sobierajska ◽  
Wojciech M. Ciszewski ◽  
Malgorzata Bukowiecka-Matusiak ◽  
Dorota Szczesna ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Original Data ◽  
Pleural Mesothelioma ◽  
Dependent Manner ◽  
Evening Primrose ◽  
Prognostic Features ◽  
Isopropanol Extract ◽  
Cycle Arrest ◽  
M Phase ◽  
First Time

Extracts from the defatted evening primrose (Oenothera paradoxa Hudziok) seeds are the source of a range of stable polyphenolic compounds, including ellagic acid, gallic acid, and catechin. Our studies evaluate, for the first time, the influence of evening primrose isopropanol extract (EPE) on malignant pleural mesothelioma (MPM) cells. MPM is rarely diagnosed, its high aggressiveness and frequently noted chemoresistance limit its treatment schemes and it is characterized by low prognostic features. Here, we demonstrate that EPE inhibited MPM growth in a dose-dependent manner in cells with increased invasion properties. Moreover, EPE treatment resulted in cell cycle arrest in the G2/M phase and increased apoptosis in invasive MPM cell lines. Additionally, EPE strongly limited invasion and MMP-7 secretion in MPM cancer cells. Our original data provide evidence about the potential anti-invasive effects of EPE in MPM therapy treatment.

Resveratrol induces cell cycle arrest and apoptosis in epithelioid malignant pleural mesothelioma cells

2017 ◽  
Vol 43 (2) ◽  
pp. 197-204
Author(s):  
Saime Batirel ◽  
Ergul Mutlu Altundag ◽  
Selina Toplayici ◽  
Ceyda Corek ◽  
Hasan Fevzi Batirel
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Malignant Pleural Mesothelioma ◽  
Cell Cycle Distribution ◽  
Pleural Mesothelioma ◽  
Dependent Manner ◽  
P53 Expression ◽  
Cycle Arrest

Abstract Background: Resveratrol is a natural anti-carcinogenic polyphenol. Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis. In this study, we investigated the effects of resveratrol on epithelioid MPM. Material and methods: Human epithelioid MPM cell line (NCI-H2452) was exposed to resveratrol (5–200 μM) for 24 or 48 h. Cell viability was assessed by WST-1 assay. Flow cytometry analyses were performed to evaluate the effects of resveratrol on cell cycle distribution and apoptosis. Western blot analysis was used to determine protein expression levels of antioxidant enzymes, cyclin D1 and p53. Reactive oxygen species (ROS) were measured using H2DCFDA. Results: Resveratrol reduced cell viability of the cells in a concentration and time dependent manner. After treatment, the cells accumulated in G0/G1 phase and the percentage of cells in G2/M phase was reduced. Resveratrol decreased cyclin D1 and increased p53 expression in cell lysates. Treated cells exhibited increased apoptotic activity. ROS were elevated with resveratrol treatment, but there was no change in the expression of superoxide dismutase (SOD)-1, SOD-2 and glutathione peroxidase. Conclusion: Our results revealed that resveratrol exhibits anti-cell viability effect on epithelioid MPM cells by inducing cell cycle arrest and apoptosis. Resveratrol may become a potential therapeutic agent for epithelioid MPM.

Effect of Metformin Intervention on Pancreatic β-Cell Apoptosis

2022 ◽  
Vol 12 (4) ◽  
pp. 873-877
Author(s):  
Dongqian Xie ◽  
Zhicheng Gao ◽  
Mei Liu ◽  
Defeng Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
High Glucose Condition ◽  
M Phase ◽  
Signaling Activation

Metformin is shown to have hypoglycemic effects. However, the relationship between metformin’s intervention in FFA-induced endoplasmic reticulum stress-mediated insulin resistance (IR) and insulin β-cell apoptosis under high-glucose condition remains unclear. Our study intends to assess their relationship. Human pancreatic β-cells were treated with metformin and cell proliferation and IR were detected by MTT assay along with detection of Wnt/β-catenin signaling by RT-PCR, cell cycle and apoptosis by flow cytometry. Metformin inhibited β cell proliferation which was mediated by FFA-induced endoplasmic reticulum stress in a time-dependent and dose-dependent manner as well as induced cell cycle arrest at G2/M phase. In addition, metformin inhibited β-catenin signaling activation and decreased the expression of c-myc, Dvl-2, survivin, Dvl-3, GSK-3β (p-ser9) and promoted GSK-3 (p-tyr216) and Axin-2 expression. In conclusion, metformin inhibits Wnt/β-catenin signaling and promotes FFA to induce endoplasmic reticulum stress, thereby mediating pancreatic β-cells behaviors.

scholarly journals Multitasking C2H2 Zinc Fingers Link Zac DNA Binding to Coordinated Regulation of p300-Histone Acetyltransferase Activity

2006 ◽  
Vol 26 (14) ◽  
pp. 5544-5557 ◽  
Author(s):  
Anke Hoffmann ◽  
Thomas Barz ◽  
Dietmar Spengler
Keyword(s):  
Dna Binding ◽  
Histone Acetyltransferase ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
C Terminus ◽  
First Time ◽  
Recruitment Model ◽  
Histone Acetyltransferase Activity

ABSTRACT Zac is a C2H2 zinc finger protein that regulates apoptosis and cell cycle arrest through DNA binding and transactivation. The coactivator proteins p300/CBP enhance transactivation through their histone acetyltransferase (HAT) activity by modulating chromatin structure. Here, we show that p300 increases Zac transactivation in a strictly HAT-dependent manner. Whereas the classic recruitment model proposes that coactivation simply depends on the capacity of the activator to recruit the coactivator, we demonstrate that coordinated binding of Zac zinc fingers and C terminus to p300 regulates HAT function by increasing histone and acetyl coenzyme A affinities and catalytic activity. This concerted regulation of HAT function is mediated via the KIX and CH3 domains of p300 in an interdependent manner. Interestingly, Zac zinc fingers 6 and 7 simultaneously play key roles in DNA binding and p300 regulation. Our findings demonstrate, for the first time, that C2H2 zinc fingers can link DNA binding to HAT signaling and suggest a dynamic role for DNA-binding proteins in the enzymatic control of transcription.

scholarly journals Glucocappasalin Induces G2/M-Phase Arrest, Apoptosis, and Autophagy Pathways by Targeting CDK1 and PLK1 in Cervical Carcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangya Xu ◽  
Xueling Yan ◽  
Zhongjia Hu ◽  
Lulu Zheng ◽  
Ke Ding ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
M Phase

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.

Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells

2011 ◽  
Vol 236 (11) ◽  
pp. 1351-1359 ◽  
Author(s):  
Chandeshwari Chilampalli ◽  
Ruth Guillermo ◽  
Radhey S Kaushik ◽  
Alan Young ◽  
Gudiseva Chandrasekher ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skin Cancer ◽  
Cell Cycle Arrest ◽  
Squamous Carcinoma ◽  
Ultraviolet B ◽  
Dependent Manner ◽  
A431 Cells ◽  
Squamous Carcinoma Cells ◽  
Cycle Arrest ◽  
M Phase

Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 μmol/L concentration induced G0/G1 cell cycle arrest significantly ( P < 0.05) and decreased the percentage of cells in the S and G2/M phase. Honokiol down-regulated the expression of cyclin D1, cyclin D2, Cdk2, Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis.

Chemosensitivity of newly established human malignant pleural mesothelioma cells: Significant growth inhibition by amrubicin, a novel 9-aminoanthracycline, or cyclooxygenase 2 inhibitor

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19060-e19060
Author(s):  
T. Hida ◽  
S. Ogawa ◽  
J. Park ◽  
J. Park ◽  
J. Shimizu ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cell Lines ◽  
Malignant Pleural Mesothelioma ◽  
Malignant Mesothelioma ◽  
Cyclooxygenase 2 ◽  
Pleural Mesothelioma ◽  
Dependent Manner ◽  
Promising Therapeutic Approach ◽  
Cyclooxygenase 2 Inhibitors

e19060 Background: Malignant pleural mesothelioma is asbestos-related malignancy that is highly resistant to current therapeutic modalities. Survival of patients with malignant mesothelioma is very poor, especially in advanced stage, regardless of a recent advancement of chemotherapeutical modalities of combination with cisplatin and antifolate. Methods: Eleven cell lines derived from malignant mesothelioma were established in our laboratory. Chemosensitivity of these cell lines to nine chemotherapeutic drugs (cisplatin, vinorelbine, irinotecan, gemcitabine, pemetrexed, gefitinib, erlotinib, and amrubicin and its active in vivo substance, amrubicin-13-OH) and four cyclooxygenase 2 inhibitors was tested by MTT assay. Results: Anti-cancer agents, cisplatin, vinorelbine, gemcitabine, gefitinib, or erlotinib, showed little growth inhibition, and pemetrexed and irinotecan showed modest growth inhibition in malignant mesothelioma cells, whereas amrubicin-13-OH showed strong growth inhibition. Cyclooxygenase 2 inhibitors inhibit proliferation of malignant mesothelioma cells in a dose-dependent manner: modest growth inhibition at clinically achievable low concentrations and complete growth inhibition at clinically achievable high concentrations by intrapleural instillation. In addition, enhanced growth suppression was obtained by using amrubicin-13-OH in combination with cyclooxygenase 2 inhibitor. Conclusions: Our study suggests that amrubicin can inhibit proliferation of malignant mesothelioma cells. In addition, the use of a cyclooxygenase 2 inhibitor may be a promising therapeutic approach in the treatment of mesothelioma, because previous studies indicated the presence of increased cyclooxygenase 2 expression in malignant mesothelioma, which is notoriously resistant to chemotherapy. No significant financial relationships to disclose.

scholarly journals Sulforaphane-N-Acetyl-Cysteine Induces Autophagy Through Activation of ERK1/2 in U87MG and U373MG Cells

2018 ◽  
Vol 51 (2) ◽  
pp. 528-542 ◽  
Author(s):  
Han-Jie Liu ◽  
Lei Wang ◽  
Lin Kang ◽  
Juan Du ◽  
Sha Li ◽  
...  
Keyword(s):  
Erk Pathway ◽  
Erk Activation ◽  
Cycle Arrest ◽  
Brain Barrier Permeability ◽  
M Phase ◽  
Apoptosis Assay ◽  
Acetyl Cysteine ◽  
Underlying Mechanisms ◽  
Interfering Rna ◽  
First Time

Background/Aims: Sulforaphane-N-acetyl-cysteine (SFN-NAC) is a sulforaphane (SFN) metabolite with a longer half-life and better blood–brain barrier permeability than those of SFN. Previous studies have found that SFN-NAC can act via ERK to destroy microtubules and inhibit cell growth in lung cancer cells. However, the underlying mechanisms are unclear, and it is unknown whether SFN-NAC can inhibit the growth of glioma. Here, we have demonstrated for the first time that SFN-NAC activates autophagy-mediated downregulation of α-tubulin expression via the ERK pathway. Methods: U87MG and U373MG cells, two widely used glioma cell lines, were utilized in this study. Apoptosis assay, western blot analysis, co-immunoprecipitation, immunostaining, and electron microscopy were used to analyze the effect of SFN-NAC on α-tubulin and its interaction with microtube-associated protein 1 light-chain 3 (LC3). Results: SFN-NAC induced cell-cycle arrest in the G2/M phase and dose-dependently induced intracellular ERK activation, autophagy, and α-tubulin downregulation. These SFN-NAC-induced effects were reversed by inhibiting the ERK pathway with its inhibitor PD98059. U87MG and U373MG cells were transfected with LC3 small interfering RNA, and the subsequent inhibition of autophagy reversed the downregulation of α-tubulin by SFN-NAC. Furthermore, co-immunoprecipitation experiments and confocal microscopy confirmed that SFN-NAC promotes the binding of LC3 with α-tubulin in the cytoplasm. Cell viability experiments demonstrate that SFN-NAC inhibits the growth of U87MG and U373MG cell colonies. Conclusion: These findings suggest that SFN-NAC is a novel potential anti-glioma agent.

scholarly journals Phosphatidylinositol Induces Caspase-Independent Apoptosis of Malignant Pleural Mesothelioma Cells by Accumulating AIF in the Nucleus

2015 ◽  
Vol 36 (3) ◽  
pp. 1037-1048 ◽  
Author(s):  
Shingo Kanemura ◽  
Ayako Tsuchiya ◽  
Takeshi Kanno ◽  
Takashi Nakano ◽  
Tomoyuki Nishizaki
Keyword(s):  
Cell Lines ◽  
Malignant Pleural Mesothelioma ◽  
Mitochondrial Membrane ◽  
Membrane Potentials ◽  
Antitumor Action ◽  
Tunel Staining ◽  
Pleural Mesothelioma ◽  
Nuclear Staining ◽  
Dependent Manner ◽  
Dapi Staining

Background/Aims: Phosphatidylinositol (PI) regulates a variety of cell processes. The present study investigated the antitumor action of 1,2-dioleoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DOPI) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DPPI) on human malignant pleural mesothelioma (MPM) cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells. Methods: MTT assay, TUNEL staining, flow cytometry using propidium iodide (PI) and annexin V (AV), enzymatic caspase assay, and nuclear staining using DAPI were carried out, and mitochondrial membrane potentials and intracellular distribution of apoptosis-inducing factor (AIF) were monitored in cells with and without the siRNA silencing the Bid-targeted gene. Results: Both DOPI and DPPI reduced cell viability for all the investigated MPM cell lines in a concentration (0.01-100 µM)-dependent manner. DOPI and DPPI significantly increased TUNEL-positive cells and the population of PI-negative/AV-positive and PI-positive/AV-positive cells, corresponding to early apoptosis and late apoptosis/secondary necrosis, respectively. DOPI and DPPI perturbed mitochondrial membrane potentials in MSTO-211H cells, but no significant activation of caspase-3, -4, -8, and -9 was obtained. DOPI and DPPI upregulated expression of Bid in MSTO-211H cells. DOPI and DPPI significantly increased nuclear localization of AIF without affecting expression of the mRNAs and proteins in MSTO-211H cells, which was inhibited by knocking-down Bid. In the DAPI staining, nuclear fragmentation and condensation were found. Conclusion: The results of the present study indicate that DOPI and DPPI facilitate Bid-mediated AIF release from the mitochondria, to accumulate AIF in the nucleus and induce caspase-independent apoptosis of MPM cells.

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