Louisiana Research Day Program Book 2025

Biomedical Research: Section 1

Biomedical Research: Section 1

Malvina Kartamyshev, OMS-III; Tanya Kumar, OMS-IV; Dalal Dawud, B, Pharm; Zakaria Abd Elmageed, PhD VCOM-Louisiana; Department of Biomedical Science, Discipline of Pharmacology, Monroe, LA 14 EXPLORING THE ANTICANCER EFFECTS OF CAMBINOL ON CASTRATION-RESISTANT PROSTATE CANCER: AN IN VITRO STUDY

Nicholas Cabral, OMS-II; Ajani Hodges, MPH; Kennedy Barlow, BS; Jana Lampe, PhD; Jamboor Vishwanatha, PhD; Amalendu Ranjan, PhD University of North Texas Health Science Center, Fort Worth, Texas, USA 15 FORMULATION AND CHARACTERIZATION OF HIGHLY WATER-SOLUBLE DOXORUBICIN LOADED POLY(LACTIDE-CO GLYCOLIDE) NANOPARTICLES FOR CANCER THERAPY

Background: Prostate cancer (PCa) is the most common cancer in men worldwide as well as the second leading cause of cancer mortality in American men, necessitating the exploration of novel therapeutic agents to combat its progression. This study highlights the effect of anti-neutral sphingomyelinase 2 (n-SMase2), Cambinol, a promising compound with potential anticancer properties on metastatic castration resistant prostate cancer (mCRPC) cells. Methods: Our study employs a multi-pronged approach, including functional and molecular assays. Metastatic CRPC cells (CWR-R1-Ca and PC-3M) were cultured and exposed to increasing concentrations of Cambinol. Cell cytotoxicity was assessed to determine the IC50 of Cambinol. The effect of Cambinol on the clonogenic potential of mCRPC cells was performed; the number and size of colonies post-treatment were analyzed. The migratory potential in response to Cambinol treatment was evaluated through scratch and transwell assays. The protein expression of n-SMase2, p-Akt, mTOR, and p-mTOR, among others, was assessed using immunoblotting analysis.

Results: Our findings reveal that Cambinol treatment significantly inhibits the viability of CWR-R1-Ca and PC-3M cells in a dose dependent manner, highlighting its potential as an antiproliferative agent. The colony formation assay results support the hypothesis that Cambinol hinders the clonogenic potential of these cells. Furthermore, a substantial reduction in cell migration upon Cambinol treatment was observed, suggesting its ability to impede metastatic potential at an early stage. Western blot analysis demonstrates alteration in the expression levels of NF-kB, p-Akt, n-SMase2, mTOR, and p-mTOR, suggesting their involvement in Cambinol’s mechanism of action against mCRPC cells. Conclusions: Our comprehensive analysis underscores the potential therapeutic effect of Cambinol in mitigating mCRPC progression. This study provides novel insights into the multifaceted effects of Cambinol on aggressive PCa cells, encompassing reduced cell viability, migration, and colony-forming abilities. These findings warrant further investigations into the antitumor effect of Cambinol using preclinical mCRPC models.

Keywords: Metastatic castration resistant prostate cancer, anti-nSMase2, Cambinol, cell proliferation, migration

Background: Cancer treatment using chemotherapy drugs results in severe side effects. To improve chemotherapy and reduce its adverse effects, nanoparticles are a promising tool to transport chemotherapeutic drugs effectively to specific cancer cells and avoid healthy tissue. These drugs are able to enter into tumors due to the nanoparticles’ minute size, taking advantage of the enhanced permeability and retention effect. By utilizing nanoparticles, we will be able to successfully deliver a high percentage of our drug, doxorubicin (Dox), into prostate cancer cells (PC3). Nanoparticles are developed through a process of multi-step emulsifications, known as water-in-oil in water (w/o/w) emulsion. Our hydrophilic drug, Dox, is first emulsified with the poly(lactide-co-glycolide) (PLGA) solution to form primary (w/o) emulsion. This primary emulsion is further emulsified with a surfactant to prepare w/o/w emulsion. Nanoparticle size and concentration were determined by using dynamic light scattering and nanoparticle tracking analysis methodologies, respectively. In vitro cellular uptake assay using fluorescent imaging were performed in PC3 cancer cell lines in order to observe the uptake efficiency

of the nanoparticles. The nanoparticles were successfully prepared containing encapsulating the hydrophilic drug doxorubicin using the water-in-oil in water emulsion technique. The particle size was determined to be 165.98 ±1.86 nm and the polydispersity index (PDI) was .075 ±.011. The concentration of the nanoparticles were found to be 1.99E+09 particles/ml and 1.82E+09 particles/ml for the blank and Dox loaded nanoparticles, respectively. Stability studies showed no major changes in the particle size and PDI when stored at 4°C. Through fluorescent imaging, it was determined that effective drug delivery was achieved into the PC3 cell line. This finding was established from the thorough visibility of Nile red stained PLGA nanoparticles within the cancer cells. Nanoparticles are effective and efficient transports, particularly when applied to cancer therapy treatments. Our nanoparticles showed successful delivery of drugs within prostate cancer cells, thereby showing the possibility of using such nanoparticles for effective imaging and cancer therapy.

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2025 Research Recognition Day