Graduation Date

Spring 5-10-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Immunology, Pathology & Infectious Disease

First Advisor

Maher Y. Abdalla

MeSH Headings

Prostate cancer

Abstract

Prostate cancer (PC) is the second most prevalent malignancy worldwide, following lung cancer, and the fifth leading cause of cancer-related mortality. Despite advancements in treatment, there remains a critical need for novel therapeutic strategies. In this study, we investigated the effects of Heme Oxygenase-1 (HO-1) modulation using pharmacological agents on the expression patterns of metabolites and amino acids in PC cells. We further explored the impact of administering selected metabolites and amino acids in combination with HO-1 inhibition on PC cell survival.

Using an in vitro model, we evaluated the effects of arginine (Arg) and glutamine (Glu), both individually and in combination with HO-1 inhibition, on tumor cells progression, cell proliferation, and migration. Additionally, we assessed the influence of HO-1 inhibition in PC mouse tissues on the expression of key enzymes involved in Arg and Glu metabolism.

Our results demonstrated that supplementation with Arg and Glu, alone or in combination with HO-1 inhibition, significantly reduced proliferation and migration in the LNCaP and DU145 human PC cell lines. Notably, LNCaP models localized PC while DU145 reflects a more aggressive, metastatic phenotype.

Furthermore, HO-1 knockdown enhanced the sensitivity of both cell lines to the chemotherapeutic agent docetaxel (Doc), both as a standalone and in combination with Arg and Glu supplementation.

These findings suggest that targeting amino acid metabolism through Arg and Glu supplementation, alongside HO-1 inhibition, may represent a promising therapeutic avenue for improving PC treatment outcomes.

Comments

2025 Copyright, the authors

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