Ferroptosis Induction Therapy for Castration Resistant Prostate Cancer
Board Location: #51
Discipline: Biological Sciences
Subcategory: Cancer Research
Session: 3
Mojisoluwa Awolowo - Morgan State University
Co-Author(s): Precious Dike, PhD , Morgan State University, Baltimore, Maryland; Valerie Odero-Marah, PhD, Morgan State University, Baltimore, Maryland
Prostate cancer (PCa) is the most common non-skin cancer in men, and second leading cause of death. The fundamental treatment for treating PCa is androgen deprivation therapy which is an effective form of treatment initially. Nevertheless, the disease reoccurs in most men; this is referred to as castration-resistant PCa (CRPC), for which the standard treatment is enzalutamide. However, some develop resistance to this enzalutamide anti-androgen agent. Ferroptosis is an iron-dependent lipid peroxidation form of regulated cell death being investigated as a novel potential therapy for PCa using ferroptosis inducers such as RSL3; they have shown promise in selectively triggering cell death in cancer cells while sparing healthy tissues. We hypothesize that RSL3- induced ferroptosis will overcome enzalutamide resistance in PCa cells. To test this, we utilized C4-2B MDVR cells which represents a cell model for aggressive PCa that metastasized to the bone and is resistant to both castration therapy and the enzalutamide drug treatment. C42B-MDVR cells were treated with increasing concentrations of RSL3 followed by analysis of cell viability with MTS assay. A dose dependent reduction in cell viability was observed which was reversed by ferroptosis inhibitor, ferrostatin-1. Western blot analysis revealed a decreased expression of the antioxidant enzyme glutathione peroxidase 4 (GPX4) with ferroptosis induction indicating a mechanism of the RSL3-induced cell death. The limitations to our research are that the research was performed in vitro and have not been tested on mouse models to visualize the effects of the treatments in animals. In conclusion, ferroptosis inducer RSL3 decreases GPX4 expression and decreases proliferation of PCa cells while ferrostatin-1 reverses the effects of the RSL3 treatment. Thus, ferroptosis inducers present a potential novel therapeutic approach for CRPC patients who have developed resistance to conventional androgen therapies.
Funder Acknowledgement(s): NIH NIGMS RISE 5R25GM058904 ;NIH/NIMHD U54MD007590; U54MD013376
Faculty Advisor: Dr Valerie Odero-Marah, valerie.odero-marah@morgan.edu
Role: All of the research to be presented was done by me. This includes but is not limited to procedures such as western blot, proliferation assay, cell culture, etc. Analysis of my data was also done by me.