Dataset Information

Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells.

ABSTRACT: Heme oxygenase-1 (HO-1) is induced by a variety of stimuli and plays a multifaceted role in cellular protection. We have shown that HO-1 is overexpressed in thyroid cancer and is associated with tumor aggressiveness. Therefore, we set out to assess the effects of HO-1 inhibitors on the biology of thyroid cancer cells. Two different classes of HO-1 inhibitors were used, including a metalloporphyrin, zinc protoporphyrin-IX (ZnPP), and an azole antifungal agent, ketoconazole. The viability and colony formation of thyroid cancer cells decreased in a concentration- and time-dependent fashion following treatment with HO-1 inhibitors. Cancer cells exhibited a higher sensitivity to HO-1 inhibitors than non-malignant cells. HO-1 inhibitors induced a G0/G1 arrest accompanied by decreased cyclin D1 and CDK4 expressions and an increase in levels of p21 and p27. HO-1 inhibitors significantly increased intracellular ROS levels and suppressed cell migration and invasion. Oxygen consumption rate and mitochondrial mass were increased with ZnPP treatment. Mice treated with ZnPP had a reduced xenograft growth and diminished cyclin D1 and Ki-67 staining in tumor sections. Taken together, HO-1 inhibitors might have therapeutic potential for inducing cell cycle arrest and promoting growth suppression of thyroid cancer cells in vitro and in vivo.

SUBMITTER: Yang PS

PROVIDER: S-EPMC6163304 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells.

Yang Po-Sheng PS Hsu Yi-Chiung YC Lee Jie-Jen JJ Chen Ming-Jen MJ Huang Shih-Yuan SY Cheng Shih-Ping SP

International journal of molecular sciences 20180824 9

Heme oxygenase-1 (HO-1) is induced by a variety of stimuli and plays a multifaceted role in cellular protection. We have shown that HO-1 is overexpressed in thyroid cancer and is associated with tumor aggressiveness. Therefore, we set out to assess the effects of HO-1 inhibitors on the biology of thyroid cancer cells. Two different classes of HO-1 inhibitors were used, including a metalloporphyrin, zinc protoporphyrin-IX (ZnPP), and an azole antifungal agent, ketoconazole. The viability and colo ...[more]

PMID: 30149527

Similar Datasets

Project description:BackgroundWe have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line.MethodsThe growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model.ResultsThe 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth.ConclusionThe 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth both in vitro and in vivo. Our findings provide a rationale for combining 225-NP with other DNA-damaging agents for achieving enhanced anticancer activity.

Dataset Information

Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells.

Publications

Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets