C-terminal-truncated and full length hemeoxygenase-1 exert opposite behavior of head and neck cancer cells

MASCARÓ, MARILINA; FERRONATO, MARIA JULIA; GANDINI, NORBERTO ARIEL; ALONSO, EXEQUIEL GONZALO; COLÓ, GEORGINA PAMELA; ALONSO, ELIANA NOELIA; GUEVARA, JOSEFINA ALEJANDRA; CURINO, ALEJANDRO CARLOS; RECIO, SERGIO; PICHEL, PAMELA; FACCHINETTI, MARIA MARTA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

We previously reported that hemeoxygenase-1 (HO-1)protein is up-regulated in human HNSCC samples and that it is localized in thecytoplasmic and nuclear compartments. We also reported that high expression ofHO-1 mRNA is associated with worst survival and that pharmacological activationof HO-1 by hemin increases viability of HN13 cells. However, how full length (FL-HO1)and C-terminal truncated (t-HO1) HO-1 affect HNSCC remains elusive. In thisstudy, we aim to elucidate if such forms of HO-1 impact on head and neck cancercells behavior. We established the FL-HO1 and t-HO1 overexpressing HN13 cells.We evaluated cell viability by crystal violet method, cell cycle progression bypropidium iodide staining and flow cytometry, and cell migration by woundhealing assay. In addition to our previous results using hemin, we found that80uM hemin increased cell number in S- (p<0,001) and G2/M (p<0,001)phases and diminished cell number in Go/G1 phase (p<0,001) at 72h. We alsofound that hemin delayed cell migration (p<0,01) respect to control. On thecontrary, at same conditions, hemin failed to increase cell viability(p>0,05) neither alters cell cycle progression (p>0,05) in the normal keratinocytecell line, HaCaT. By a genetic approach, we found that FL-HO1 HN13 cells have ahigher growth rate (p<0,001) than its control and cell cycle progression isas similar as (p<0,001 vs control) it was observed with hemin treatment.However, FL-HO1 failed to alter migratory capacity (p>0,05). We also found that t-HO1 expression impaired HN13 cellviability (p<0,01 vs FL-HO1 HN13) and induced a Go/G1 arrest (p<0,01) anda diminished cell number in SubGo (p<0,01) and S- (p<0,05) phases. Also,we found that t-HO1 expression delayed cell migration (p<0,001) respect toFL-HO1 HN13. In conclusion, our results show that head and neck cancer cellssurvival, cell cycle progression and migration capacity depends on predominantHO-1 form.