INHIBITION OF SPHINGOMYELINASE 2 DECREASES CELL PROLIFERATION AND MIGRATION IN AGGRESSIVE PROSTATE CANCER CELLS
Tanya Kumar, Malvina Kartamyshev, Dalal Dawud, B. Pharm, Roopin Singh, Kareem Abdulhamid, Yao Liang, Abir Islam, Hassan Khanani, Murtaza Khambhati, Wasifuddin Syed, Hassan Ebrahim, Zakaria Abd Elmageed; Louisiana State University School of Medicine, New Orleans, LA.
Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive form of prostate cancer (PCa), and its treatment remains an unmet clinical need. Further studies are needed for the exploration of novel therapeutic strategies to manage the disease. The current study highlights the effect of Cambinol, a specific inhibitor of neutral sphingomyelinase 2 (n-SMase2), as a promising compound with potential antitumor properties on mCRPC cells. Methods/Results: mCRPC cells were treated with different concentrations of Cambinol for 72 hours. Cell viability assay was deployed to determine the IC50 of Cambinol. The effect of the drug on the clonogenic potential was also performed. The migratory potential of cancer cells in response to Cambinol treatment was evaluated by a scratch assay. The protein expression and activity of NF-κB, ERK1/2, and n-SMase2 were assessed using immunoblotting
analysis. Our findings demonstrate that treatment with Cambinol significantly inhibited mCRPC cell viability in a concentration-dependent manner, highlighting its potential as an antiproliferative agent. Results from the colony formation assay support the hypothesis that Cambinol hinders the clonogenic potential of these cells. A substantial reduction in cell migration upon Cambinol treatment was observed, suggesting its ability to impede the metastatic potential of mCRPC cells. Immunoblotting analysis demonstrated a decreased expression in NF-κB, n-SMase2, and phosphorylation of ERK1/2. Discussion: This study provides new insights into the multifaceted effects of Cambinol on mCRPC cells, encompassing reduced cell viability, colony formation, and cell migration. These findings suggest a promising novel approach for the treatment of mCRPC using Cambinol and warrant further investigations in preclinical settings.
TORSADE’S AND TRIGGERS: NAVIGATING QTC PROLONGATION IN HIV-RELATED CRYPTOCOCCAL INFECTION
Thomas Tran, Asad Mussarat, Charlie Woodall, Rasha Kako, Thomas Cranfill, Cole Rogers, Cole Pittman, Michael Modica; Louisiana State University School of Medicine, New Orleans, LA.
Introduction: QTc prolongation is a cardiac arrhythmia that can lead to life-threatening complications, including Torsades de pointes (TdP) and cardiac arrest. This arrythmia is triggered by various factors, including electrolyte imbalances, medications, and underlying infections such as human immunodeficiency virus (HIV). Case: A 52-year-old man with untreated HIV presented with fever, chills, and generalized weakness. He was found to have disseminated cryptococcus bacteremia and meningitis and completed induction therapy with amphotericin B and flucytosine. He was ultimately transitioned to maintenance dose fluconazole. Five weeks later, the patient had an 8-minute cardiac arrest with pulseless electrical activity with eventual return of
spontaneous circulation. A electrocardiogram (EKG) following the arrest showed sinus rhythm with a QTc interval of 380 milliseconds. The patient showed significant recovery after extubation but shortly after became unresponsive with a sinus rhythm devolving into TdP. His QTc intervals on subsequent EKGs ranged from 465 – 700 m/s. Fluconazole was held, and all other QTc prolonging agents were avoided. A coronary angiogram appreciated no signs of coronary artery disease. A CT of the chest did not appreciate an acute pulmonary embolism. The patient received several grams of magnesium sulfate throughout the remainder of his hospital course and was placed on isoproterenol infusion along with a transvenous pacer. However, despite attempts for cardiac stabilization, he experienced three more cardiac arrest events, two of them including 71
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