Louisiana Via Research Day Book 2026

Biomedical Research: Section 2

Biomedical Research: Section 2

Md Towhidul Islam Tarun, MS 1 ; Hassan Y. Ebrahim, PhD 1,2 ; Khalid A. El Sayed, PhD 1* 1 College of Pharmacy, University of Louisiana at Monroe; 2 VCOM-Louisiana 24 THE OLIVE PHENOLIC S-(-)-HYDROXYOLEOCANTHAL ATTENUATES NEUROENDOCRINE PROSTATE CANCER VIA MODULATION OF EPHA3-CENTERED ONCOGENIC NETWORK

Md Ashiq Mahmud, MSc 1 ; Mohamed M Mohyeldin, PhD 2 ; Md Towhidul Islam Tarun, MSc 1 ; Judy A. King, PhD 3 ; Hassan Y. Ebrahim, PhD 4 ; Khalid A. El Sayed, PhD 1 1 Department of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe; 2 Alexandria University, Alexandria, Egypt; 3 Lincoln Memorial University, Knoxville, Tennessee; 4 VCOM-Louisiana 25 TARGETING IL-17A–DRIVEN TRIPLE-NEGATIVE BREAST CANCER PROGRESSION AND RECURRENCE USING NOVEL NATURAL PRODUCTS.

Background: Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC). The receptor tyrosine kinase EPHA3 is a critical driver for NEPC. It is overexpressed in PCa, particularly in androgen-independent and neuroendocrine subtypes. EPHA3 activates c-Myc signaling to enhance EZH2 expression, promoting histone H3K27 trimethylation. The neural transcription factor BRN2 functions upstream of both EZH2 and ASCL1. The latter regulates the Notch pathway ligand DLL3, thereby orchestrating neuroendocrine differentiation. Elevated expression of classical neuroendocrine markers CHGA and SYP is characteristic of the NEPC phenotype. This study reports the novel usage of the olive phenolic S-(-)-hydroxyoleocanthal (HOC, oleacein) to effectively control NEPC by targeting the EPHA3–BRN2–EZH2–ASCL1– DLL3–SYP–CHGA oncogenic network.

Methods: Cell viability assays were conducted to assess in vitro effects. To model NEPC progression and recurrence, NCI-H660-Luc cells were xenografted into male athymic nude mice. RNA-sequencing was performed to compare the differentially expressed genes between placebo control and treated tumors. Results: HOC significantly attenuated the proliferation of NEPC NCI-H660 cells in vitro. Daily oral administration of HOC at 10 mg/ kg body weight markedly suppressed the progression of NEPC NCI-H660-Luc tumors. Continued HOC treatments after surgical excision of the primary tumors substantially reduced locoregional recurrence. HOC significantly downregulated the expression of EPHA3, BRN2, EZH2, ASCL1, DLL3, SYP, and CHGA in treated primary and recurrence tumors versus placebo control. Conclusion: These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC.

Context: Triple-negative breast cancer (TNBC) is aggressive malignancy lacking targeted therapeutic options and is associated with high rates of progression, recurrence and mortality. Chronic inflammation within the tumor microenvironment, particularly mediated by interleukin-17A (IL-17A), contributes to TNBC proliferation, angiogenesis, and treatment resistance, highlighting IL-17A signaling as a promising therapeutic target. Problem: Despite growing evidence linking IL-17A to TNBC aggressiveness, clinically viable small-molecule inhibitors capable of disrupting IL-17A-driven oncogenic signaling remain limited. Natural products offer a rational framework for discovery and development of anti-inflammatory anticancer entities with improved anti-TNBC potency. Objective: This study aimed to determine whether rationally designed novel podocarpic acid–based esters can suppress IL-17A mediated TNBC progression and recurrence by inhibiting downstream oncogenic signaling pathways.

Methods: Structure-based molecular docking was performed against IL-17A (PDB ID

of IL-17A downstream signaling components, supporting on-target anti-TNBC activity. Statistical significance was observed across key endpoints. Conclusions: Tyrosol podocarpicate effectively suppresses IL-17A-driven TNBC progression and recurrence through inhibition of downstream signaling effectors, proliferation, and vasculogenesis. This study validates cytokine mediated TNBC pathogenesis targeting as a viable therapeutic strategy.

7AMA) to evaluate binding interactions. In vitro assays assessed cell viability, clonogenicity, migration, and IL-17A responsiveness in TNBC cell lines. Orthotopic xenograft studies were conducted in female nude mice to evaluate IL-17A-driven TNBC pathogenesis. Serum CA 15-3 levels were quantified by ELISA. Tumor tissues were analyzed by immunofluorescence for Ki-67 and CD31 expression, histopathology, and Western blotting to assess downstream IL-17A signaling pathway modulation by tyrosol podocarpate treatments. Results: Tyrosol podocarpate demonstrated strong interference with IL-17A homo and heterodimerization with IL-17F and significantly inhibited IL-17A-induced TNBC cell proliferation and migration. In orthotopic nude mouse xenograft models, treatment markedly reduced tumor growth and recurrence, accompanied by decreased serum CA 15-3 levels. Immunofluorescence analysis revealed reduced Ki-67 and CD31 expression in treated tumors. Western blot analysis confirmed downregulation

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2026 Research Recognition Day