Can diallyl trisulfide, a dietary garlic-derived compound, activate ferroptosis to overcome therapy resistance in prostate cancer?

Abstract

Background: Therapy resistance is the underlying reason for poor outcome in prostate cancer (PCa) patients. Diallyl trisulfide (DATS) is an organosulfur compound present in garlic. DATS has been shown to target PCa cells by induction of apoptosis, increase in the production of reactive oxygen species, degradation of ferritin protein and increase in the labile iron (Fe) pool. Aim: We hypothesize that DATS could induce ferroptosis, an Fe-dependent, unique non-apoptotic form of regulated cell death to eliminate therapy resistance encountered by PCa patients. Methods: In vitro and in vivo studies should be performed to test the hypothesis. Results: As per the hypothesis, DATS would eliminate apoptotic resistance via inducing ferroptosis. Conclusion: Since apoptosis resistance has been reported to be the underlying mechanism of therapy resistance in PCa, DATS could be used to effectively target PCa cells by overcoming apoptosis resistance and inducing ferroptosis-mediated cell death of PCa cells.