VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 1

Malvina Kartamyshev, OMS-II; Hassan Khanani, OMS-II; Roopin Singh, OMS-II; Abir Islam, OMS-II; Yao Liang, OMS-II; Kareem Abdelhamid, OMS-II; Wasifuddin Syed, OMS-II; Murtaza Khambhati, OMS-II; Tanya Kumar, OMS-III; Dalal Dawud, BPharm; Zakaria Abd Elmageed, PhD VCOM-Louisiana 2 SYNERGISTIC EFFECT OF CAMBINOL AND APALUTAMIDE ON METASTATIC CASTRATION-RESISTANT PROSTATE CANCER CELLS

Background: Metastatic castration-resistant prostate cancer (mCRPC) poses a significant clinical challenge due to its resistance to conventional therapies. Targeting multiple pathways is one of the effective options to manage patients with mCRPC. Objective: In this study, we explored the potential synergistic effects of Cambinol, a specific inhibitor of neutral sphingomyelinase 2 (n-SMase 2), and Apalutamide, a potent antagonist of phosphorylated AKT (phospho AKT), on mCRPC cell lines; CWR-R1ca and PC-3M. Methods: Our investigation employed a multidimensional approach, combining MTT assays, colony formation assays, scratch assays, and Western blot analysis to comprehensively evaluate the therapeutic effect of the drug combination. Results: The MTT assay revealed a notable reduction in cell viability upon treatment with the combined Cambinol and Apalutamide, indicating a synergistic anti-proliferative effect. Colony formation assays further demonstrated a significant suppression of clonogenic potential, suggesting a potential impairment of the cells’ ability to form colonies. Scratch

assays elucidated a pronounced inhibition of cell migration, emphasizing the potential role of the combined drugs to impede metastatic processes in mCRPC cells. To elucidate the molecular mechanisms underlying these observed effects, Western blot analysis shows that Cambinol demonstrated an inhibition of sphingomyelinase activity, while Apalutamide effectively suppressed phospho-AKT activity. Conclusions: Our findings provide compelling evidence for the synergistic anti-cancer effects of Cambinol and Apalutamide on mCRPC cells, highlighting the potential of this combination as a promising therapeutic strategy. This study suggests a dual-targeted approach to enhance therapeutic efficacy for treatment of patients with mCRPC.

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