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

International Journal of Molecular Sciences
Po-Sheng YangShih-Ping Cheng

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 inducin...Continue Reading

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Citations

Jun 16, 2019·International Journal of Molecular Sciences·Daniela Grimm
Aug 21, 2019·Frontiers in Endocrinology·Cedric O RenaudGerasimos P Sykiotis
Jul 24, 2020·Chemistry : a European Journal·Stepan GeriHolger Stephan
Jul 17, 2020·Molecular Cancer Research : MCR·Zeyad D NassarLisa M Butler
Dec 3, 2020·European Journal of Medicinal Chemistry·Katarzyna MalarzAnna Mrozek-Wilczkiewicz
Jan 6, 2021·International Journal of Molecular Sciences·Ayleen Fernández-FierroAlexis M Kalergis
Mar 2, 2021·ELife·Leonie ZeitlerPeter J Murray
May 27, 2021·International Journal of Endocrinology·Jie-Jen LeeShih-Ping Cheng
Jul 1, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Rong PanKe Jian Liu

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Methods Mentioned

BETA
flow cytometry
Xenograft
genotyping
Assay
electrophoresis
PCR

Software Mentioned

CellQuest Pro
ModFit LT

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