MnTE-2-PyP Suppresses Prostate Cancer Cell Growth via H₂O₂ Production

• Main Authors: Yuxiang Zhu (Author), Elizabeth A. Kosmacek (Author), Arpita Chatterjee (Author), Rebecca E. Oberley-Deegan (Author)
• Format: Book
• Published: MDPI AG, 2020-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

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 H₂O₂ levels are critical in inhibiting the growth of PC3 and LNCaP cells, but the increased H₂O₂ 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 H₂O₂ 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-G₁ 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.

Item Description

10.3390/antiox9060490
2076-3921