Louisiana Research Day Program Book 2025

Biomedical Research: Section 2

Biomedical Research: Section 2

THE MARINE-DERIVED FURANOCEMBRANOID DITERPENE SARCOPHINE SUPPRESSES METASTATIC CASTRATION RESISTANT PROSTATE CANCER PROGRESSION AND RECURRENCE VIA DOWNREGULATION OF CADHERIN-12

Oliver McGehee 1 ; Hassan Ebrahim PhD 2 ; Nehal A. Ahmed 1 ; Khalid El Sayed PhD 1 * 1 School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe LA; 2 Department of Pharmacology, Faculty for Pharmacology, VCOM, Monroe LA. MOLECULAR MECHANISTIC INSIGHTS ON THE PROSTATE CANCER RECURRENCE SUPPRESSOR LEAD PSEUROTIN A: PATHWAY ENRICHMENT AND PROTEIN INTERACTION ANALYSIS OF GENE EXPRESSION DATA 30

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Abdullah Alhowiriny 1 ; Ethar Mudhish 1 ; Hassan Y. Ebrahim, PhD 1,2 ; Khalid A. El Sayed, PhD 1 1 School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe; 2 VCOM-Louisiana

Background: Prostate cancer (PC) is one of the highest incidence malignancies among men globally, emphasizing the necessity for effective therapies. Castration-resistant prostate cancer (CRPC) continues to pose a substantial therapeutic challenge, highlighting the urgent need for effective treatment options. Oceans cover over 70% of the earth and possess 80% of Earth’s animal life. Marine natural products (MNPs) represent an unexplored resource for the discovery of lead compounds. Several MNPs and their derivatives earned the FDA approval as drug entities. MNPs possess novel chemistry since their production in marine invertebrates is intended for chemical defense or to aid animal survival against harsh environment. The diversity of MNPs clearly point to the significance of exploring marine biodiversity for novel anticancer entity discovery. This study focuses on the anti-PC activity of the cembranoid diterpene sarcophine isolated from the Red Sea soft coral Sarcophyton glaucum. A series of in vitro experiments were conducted across multiple human PC cell lines, including the androgen-independent PC-3, PC-3M, and DU-145, the androgen-dependent LNCaP and the castration-resistant recurrent CWR-R1ca

cells. Sarcophine showed significant activity against the motility of the metastatic CRPC CWR-R1ca cells, which therefore selected for the in vivo validation. CWR-R1ca-Luc cells subcutaneously xenografted into male nude mice then treated with sarcophine intraperitoneal 3x/week. Sarcophine treatment showed significantly reduction in tumor progression over 3-week period. Primary tumor surgical excision followed by continued sarcophine treatments over 8-week period. Simultaneously, sarcophine effectively suppressed both locoregional and distant tumor recurrences at bone, brain, liver, spleen, and lung. Furthermore, comprehensive transcriptomic analysis utilizing RNA sequencing of collected animal tumors identified that cadherin-12 (CDH12), a subtype of the N-Cadherin superfamily, was the gene most remarkably impacted by sarcophine treatment versus vehicle control. Study results point out CDH12 as a new molecular target for the pathogenesis of mCRPC. These findings highlight sarcophine’s potential as novel lead for the control of mCRPC progression and recurrence.

Background: The Human Genome Project was completed in 2003. It contained an extraordinary wealth of biological data waiting to be explored; however, with this myriad of genomics data came an equally huge demand for tools and methods capable of interpreting progressing biological information. Pathway enrichment analysis (PEA) is a computational biological method that interprets genome-scale (omics) experiments to help researchers identify adverse outcome pathways, gain mechanistic insights, and explore the functions of hundreds of genes in a high-throughput manor. Pseurotin A (PsA) is a fungal-derived spiro-heterocyclic γ-lactam alkaloid validated as a dual inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion and protein-protein interaction with LDLR. PsA was promoted as a lead effective for the control of castration resistant prostate cancer (CRPC) recurrence. This study utilized R and the STRINGApp 2.1.1 in Cytoscape to perform PEA and functional network analysis on RNA sequencing data gathered from PsA long-term treated and non treated recurred mCRPC tumors collected from a nude mouse xenograft model. The PEA was performed utilizing the Gene Ontology (GO) and

Kyoto Encyclopedia of Genes and Genomes (KEGG) Medicus gene sets downloaded from the gene set enrichment analysis (GSEA) database. The KEGG pathway analysis of downregulated differentially expressed genes (DEG) revealed significantly enriched pathways associated with the ubiquitin proteasome system. The functional network analysis on the downregulated DEGs also revealed a prominent network with many genes whose downregulation was implemented in promoting apoptosis, inhibiting proliferation, and reducing migration of cells. This potential pathway could hold the key to elucidating the molecular mechanism behind the PsA ability to modulate CRPC progression and recurrence. This study highlights the promise of using genomic-RNA sequencing data to guide future therapeutic and safety breakthrough discoveries in a more efficient, high-throughput, and cost effective manner.

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2025 Research Recognition Day