Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells
AbstractHeme 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. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 157 KB)
Share & Cite This Article
Yang, P.-S.; Hsu, Y.-C.; Lee, J.-J.; Chen, M.-J.; Huang, S.-Y.; Cheng, S.-P. Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells. Int. J. Mol. Sci. 2018, 19, 2502.
Yang P-S, Hsu Y-C, Lee J-J, Chen M-J, Huang S-Y, Cheng S-P. Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells. International Journal of Molecular Sciences. 2018; 19(9):2502.Chicago/Turabian Style
Yang, Po-Sheng; Hsu, Yi-Chiung; Lee, Jie-Jen; Chen, Ming-Jen; Huang, Shih-Yuan; Cheng, Shih-Ping. 2018. "Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells." Int. J. Mol. Sci. 19, no. 9: 2502.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.