Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells

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.

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Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-07-0052 ◽

2007 ◽

Vol 6 (7) ◽

pp. 1962-1972 ◽

Cited By ~ 87

Author(s):

Anne S. Tsao ◽

Dandan He ◽

Babita Saigal ◽

Suyu Liu ◽

J. Jack Lee ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Malignant Pleural Mesothelioma ◽

Migration And Invasion ◽

Pleural Mesothelioma ◽

Cycle Arrest

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Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma

10.1101/2021.02.08.430196 ◽

2021 ◽

Author(s):

Elisabet Aliagas ◽

Ania Alay ◽

Maria Martínez-Iniesta ◽

Miguel Hernández-Madrigal ◽

David Cordero ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Overall Survival ◽

Cell Cycle Arrest ◽

Malignant Pleural Mesothelioma ◽

Pleural Mesothelioma ◽

Preclinical Studies ◽

Preclinical Models ◽

Cycle Arrest

AbstractThere is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Here, we investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest thereby increasing cell senescence and increased the expression of interferon signaling pathway and tumor antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumor growth and prolonged overall survival in a platinum-naïve and platinum resistant MPM mouse model. Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.

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