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.

mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth

“…Primer sequences are shown in Table 1. 6 A. OligodT magnetic beads were used to extract siRNA and mRNA of shFUS treated LNCaP and C42 cells according to the kit, and the mRNA length was interrupted to 200 nt. Subsequently, the mRNA was incubated with antibodies and deliberately enriched, and 10% of RNA was isolated as input.…”

“…Ferroptosis is involved in regulating the pathogenesis of various urinary tumors such as PRAD, bladder cancer, and kidney cancer [ 6 ]. The most common inducer of ferroptosis is Erastin, which activates multiple pathways quickly and persistently and is suppressed by the ferroptosis disease inhibitors Fer-1, DFO, and NAC [ 5 , 6 ]. The induction of ferroptosis is related to the imbalance of oxidation level, involving excessive accumulation of reactive oxygen species (ROS) and release of oxygen free radicals, etc.…”

“…Due to the limited treatment of PRAD contemporary, it is necessary to explore its pathogenesis and provide guidance for the early diagnosis and treatment of PRAD. Ferroptosis is a nonapoptotic or autophagy death mode caused by the accumulation of iron-dependent lipid peroxides [5][6][7]. Ferroptosis is involved in regulating the pathogenesis of various urinary tumors such as PRAD, bladder cancer, and kidney cancer [6].…”

“…Ferroptosis is a nonapoptotic or autophagy death mode caused by the accumulation of iron-dependent lipid peroxides [5][6][7]. Ferroptosis is involved in regulating the pathogenesis of various urinary tumors such as PRAD, bladder cancer, and kidney cancer [6]. The most common inducer of ferroptosis is Erastin, which activates multiple pathways quickly and persistently and is suppressed by the ferroptosis disease inhibitors Fer-1, DFO, and NAC [5,6].…”

“…The induction of ferroptosis is related to the imbalance of oxidation level, involving excessive accumulation of reactive oxygen species (ROS) and release of oxygen free radicals, etc. [5][6][7][8]. At the same time, glutathione peroxidase 4 (GPX4) can inhibit peroxide under the action of glutathione (GSH), thereby inhibiting ferroptosis and promoting the growth of cancer cells [9,10].…”