HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells

• Main Authors: Florencia Cascardo, Nicolás Anselmino, Alejandra Páez, Estefanía Labanca, Pablo Sanchis, Valeria Antico-Arciuch, Nora Navone, Geraldine Gueron, Elba Vázquez, Javier Cotignola
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Antioxidants
• Subjects: <i>HMOX1</i>; HO-1; LDH; cancer metabolism; prostate cancer
• Online Access: https://www.mdpi.com/2076-3921/10/6/966

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.