Science and Technology Production
REVISTA MEDICINA - UNRAVELING THE IMPACT OF CARBON MONOXIDE-RELEASING MOLECULES ON PROSTATE CANCER CELL BEHAVIOR
Congress
Authorship:
PASCUAL, GASTÓN MARIO ; Seniuk, Rocio ; Sanchis, Pablo ; Sabater, Agustina ; Cotignola, Javier ; Vazquez, Elba ; Toro, Ayelen ; Foresti, Roberta ; Motterlini, Roberto ; Gueron, GeraldineDate:
2024Publishing House and Editing Place:
MedicinaSummary *
Carbon monoxide (CO) is a physiological gasotransmitter known for its anti-inflammatory and antioxidant properties, playing crucial roles in various cellular processes. Carbon Monoxide-Releasing Molecules (CO-RMs) have been developed to safely deliver CO to cells, showing promising therapeutic potential across multiple diseases. This study aimed to assess the effects of three water-soluble CO-RMs—CORM-3, CORM-401, and CORM-A1—on key hallmarks of prostate cancer (PCa). Using two distinct PCa cell lines, PC3 and MDA PCa 2b, we evaluated cell viability across a range of CO-RM concentrations (25-150 µM; 6 h) to identify doses that do not compromise cell viability for further analyses. Confocal microscopy with the DCFH-DA probe revealed that CO-RM treatment significantly reduced reactive oxygen species (ROS) levels in both cell lines (p<0.05). Furthermore, CO-RMs enhanced cell adhesion (p<0.05) and inhibited cell migration, particularly with CORM-3 (p<0.05). Further, mitochondrial integrity and biogenesis were signifcantly altered as shown by MitoGreen and TMRE staining. Metabolically, PC3 cells treated with CORM-401 exhibited significant reductions in ATP content, LDH activity, and LDH levels (p<0.05), while the opposite effects were observed in MDA PCa 2b cells, indicating that CO-RM effects are influenced by cell-specific characteristics. On the molecular level, CO-RMs repressed markers of oxidative stress (SOD-2), metabolism (LDH), proliferation (Ki67), and angiogenesis (VEGF) in PC3 cells (p<0.05), as assessed by RT-qPCR. This study demonstrates that CO-RMs effectively modulate key biological processes in PCa cells, highlighting their potential as therapeutic agents for PCa. Information provided by the agent in SIGEVAKey Words
CARCINOGENESISCARBON MONOXIDE RELEASING MOLECULESPROSTATE CANCERMETABOLISM