| Summary: | Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of <i>LDHA</i>, <i>LDHB</i> and <i>HMOX1</i> in PCa, identifying that high <i>LDHA</i> or low <i>LDHB</i> expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low <i>HMOX1</i> and high <i>LDHA,</i> while an improved prognosis was observed for those with high <i>HMOX1</i> and <i>LDHB</i>. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.
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