Louisiana Via Research Day Book 2026

Biomedical Research: Section 1

Biomedical Research: Section 1

Kyrillos Guirguis, OMS-II 1 ; Kendyl Berry, OMS-II 1 ; Areeba Imran, OMS-II 1 ; Maysoon Makhlouf, PhD 1 ; Grace, Lee, OMS-III 1 ; David Stephen, DO 2 ; Zakaria Y. Abd Elmageed, PhD 1 1 VCOM-Louisiana; 2 VCOM-Auburn 13 ANTIPSYCHOTIC ILOPERIDONE AS A NOVEL THERAPEUTIC CANDIDATE FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Thomas Rhett Murphrey, OMS-II; Erica Jeffress, OMS-II; Melissa EH Lipsmeyer, PhD VCOM-Louisiana 14 EXPLORING THE EFFECTS OF THE GUT MICROBIOME–DERIVED METABOLITE INDOLE-3-PROPIONIC ACID ON COLORECTAL CANCER CELL LINES OF VARYING AGGRESSIVENESS

Background: Prostate cancer (PCa) is the most frequently diagnosed malignancy in American men and is the second leading cause of cancer related mortality. Clinically, PCa is classified as either castration sensitive (CSPC) or castration resistant (CRPC) based on its response to androgen deprivation therapy (ADT), which serves as the standard first line treatment for CSPC. In CRPC, tumor progression occurs despite ADT, requiring the addition of androgen receptor pathway inhibitors and chemotherapy. As CRPC advances, these hormone based treatments often become less effective, contributing to poor clinical outcomes. This study investigates an alternative therapeutic approach aimed at mitigating metastatic CRPC (mCRPC) using in vitro and in-vivo models. Methods: Iloperidone (ILO), a second generation antipsychotic drug primarily used to treat schizophrenia, was evaluated for its potential antitumor effects on two mCRPC cells. Drug efficacy was assessed through cell survival and migration assays, including scratch wound healing and clonogenic assays to measure cell motility. A nude mouse model was also employed to investigate the effects of ILO on tumor size.

Results: Preliminary findings indicate that ILO exhibits cytotoxicity effects in PC-3M and CWR R1ca cell lines under both short- and long-term treatment conditions. Sublethal concentrations of ILO significantly reduced cell migration and invasion. Treatment of mice with ILO (1.0 mg/kg/ day, intraperitoneal) for 3 weeks reduced tumor size by 48.5% (p<0.001) compared with mice received vehicle only. Discussion: ILO showed significant anticancer activity by suppressing cell proliferation, migration, and tumor growth in a mouse model. These findings indicate that ILO could represent a promising alternative targeting strategy for mCRPC therapy. Future research will aim to assess its antitumor efficacy in combination with standard treatment options. Keywords: Castration-resistant prostate cancer, antipsychotics, iloperidone, antitumor activity, cell migration

Context: Obesity is associated with alterations in the gut microbiome that potentially lead to changes in microbial metabolite production, which can influence the initiation and progression of colorectal cancer (CRC). Indole-3-propionic acid (IPA), a tryptophan-derived microbial metabolite, is a mediator of many cellular processes dysregulated in obesity that promote cancer cell viability such as oxidative stress, glucose homeostasis and insulin signaling. With regards to CRC, IPA has previously been implicated in regulating inflammation, epithelial barrier integrity, and cancer-related signaling pathways, but its effects on obesity driven CRC cell behavior remain incompletely understood. Objective: The objective of this study is to explore how IPA affects cellular function in HCT116 (more aggressive) and HT-29 (less aggressive) CRC cell lines in an in vitro model of obesity. We further seek to determine if IPA can inhibit obesity-driven changes in cell signaling that promote cell proliferation and metastatic behavior.

Methods: For this study, we will utilize an in vitro model of obesity where CRC cell lines of varying aggressiveness are cultured in adipocyte conditioned media (ACM) to mimic an obesogenic environment for 72 hours in the presence or absence of physiological levels of IPA (1uM). Western blot and qRT PCR analyses will be conducted to determine if IPA can mitigate obesity-induced changes in cancer-related signaling pathways that alter cell proliferation, migration and apoptosis. Other enzymatic assays will be used to determine how ACM impacts cell viability and if IPA can influence these effects. Results/Anitcipated Results: Based on previous studies performed in other cancer cell types, we anticipate that ACM will promote cell viability of both aggressive and non-aggressive CRC cells which will be impeded by IPA. We further expect that IPA will normalize alterations in cancer associated signaling pathways induced by an obesogenic environment that are associated with cell proliferation, migration and invasion therefore lowering metastatic potential of more aggressive CRC cell types.

Conclusions: These findings will deepen understanding of how obesity related microbiome alterations contribute to CRC progression and may highlight IPA as a promising avenue for therapeutic intervention.

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2026 Research Recognition Day