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• W4383711205 abstract "Prostate Cancer (PCa) is the second most prevalent cancer in the world. Currently, most treatments for PCa involve Androgen Deprivation Therapy (ADT) which inhibits androgen-dependent tumor cell growth. When PCa is diagnosed early and is still Androgen Dependent, ADT is effective. However, this therapy is not effective for metastatic Castration-Resistant Prostate Cancer (mCRPC). Although the mechanism of becoming Castration-Resistant is not fully understood, it is known that high levels of oxidative stress (OS) are important for cancer suppression. Catalase is a very important enzyme in controlling OS levels. We hypothesized that catalase function is critical for the progression to mCRPC. To test this hypothesis, we used a CRISPR nickase system to create a catalase knockdown in PC3 cells, a mCRPC human-derived cell line. We obtained a Cat+/- knockdown cell line, which has approximately half of the transcripts for catalase, half of the protein levels, and half of catalase activity. The Cat+/- cells are also about twice as sensitive to H2O2 exposure compared to WT cells, migrate poorly, have low attachment to collagen, high attachment to Matrigel, and proliferate slowly. Using SCID mice for a xenograft model, we show that Cat+/- cells form smaller tumors than wild-type tumors with less collagen and no blood vessels. These results were validated via rescue experiments where functional catalase was reintroduced into the Cat+/- cells and the phenotypes were reversed. This study shows a novel role for catalase in deterring mCRPC development and points to a new potential drug target for mCRPC progression. Summary: Novel treatments for Metastatic Castration-Resistant Prostate Cancer are needed. By taking advantage of the sensitivity of tumor cells to oxidative stress (OS), reducing an enzyme, catalase, that decreases OS, has the potential to provide another target for Prostate Cancer therapy." @default.
• W4383711205 created "2023-07-11" @default.
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• W4383711205 date "2023-01-01" @default.
• W4383711205 modified "2023-09-25" @default.
• W4383711205 title "Catalase as a novel drug target for metastatic castration-resistant prostate cancer." @default.
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