Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability

• Published in: Antioxidants Vol. 11; no. 10; p. 2077
• Main Authors: Mascaró, Marilina, Alonso, Exequiel G, Schweitzer, Karen, Rabassa, Martín E, Carballido, Jessica A, Ibarra, Agustina, Alonso, Eliana N, Bermúdez, Vicente, Fernández Chavez, Lucía, Coló, Georgina P, Ferronato, María Julia, Pichel, Pamela, Recio, Sergio, Clemente, Valentina, Fermento, Maria Eugenia, Facchinetti, María Marta, Curino, Alejandro C
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-10-2022; MDPI
• Subjects: Biliverdin; Cancer; Carbon monoxide; Cell culture; Cell cycle; Cell viability; Cytoplasm; Disease; Enzymatic activity; Head & neck cancer; head and neck; Head and neck cancer; Head and neck carcinoma; Heme; Heme oxygenase (decyclizing); hemoxygenase-1; Localization; Medical research; mRNA; nucleus; Physiological aspects; Plasmids; Squamous cell carcinoma; Tumors; Vehicles; Argentina; United States > US; Taiwan
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11102077

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.