| Summary: | Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, a superoxide dismutase (SOD) mimic, is a known radioprotector of normal tissues. Our recent work demonstrated that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this study, we identified that MnTE-2-PyP-induced intracellular H<sub>2</sub>O<sub>2</sub> levels are critical in inhibiting the growth of PC3 and LNCaP cells, but the increased H<sub>2</sub>O<sub>2</sub> levels affected the two cancer cells differently. In PC3 cells, many proteins were thiol oxidized with MnTE-2-PyP treatment, including Ser/Thr protein phosphatase 1 beta catalytic subunit (PP1CB). This resulted in reduced PP1CB activity; however, overall cell cycle progression was not altered, so this is not the main mechanism of PC3 cell growth inhibition. High H<sub>2</sub>O<sub>2</sub> levels by MnTE-2-PyP treatment induced nuclear fragmentation, which could be synergistically enhanced with radiotherapy. In LNCaP cells, thiol oxidation by MnTE-2-PyP treatment was not observed previously and, similarly to PC3 cells, there was no effect of MnTE-2-PyP treatment on cell cycle progression. However, in LNCaP cells, MnTE-2-PyP caused an increase in low RNA population and sub-G<sub>1</sub> population of cells, which indicates that MnTE-2-PyP treatment may cause cellular quiescence or direct cancer cell death. The protein oxidative modifications and mitotic catastrophes caused by MnTE-2-PyP may be the major contributors to cell growth inhibition in PC3 cells, while in LNCaP cells, tumor cell quiescence or cell death appears to be major factors in MnTE-2-PyP-induced growth inhibition.
|
|---|
