Saudi Cultural Missions Theses & Dissertations
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Item Restricted Repurposing Approved-Chemotherapeutics for Head and Neck Squamous Cell Carcinoma(Saudi Digital Library, 2022) Alkurdi, Khlood; Tappuni, Anwar; Muy, Teck- TehThe advancement in head and neck squamous cell carcinoma (HNSCC) therapy necessitates the acquisition of a superior understanding of cancer molecular biology and the capability to use this knowledge to adapt the therapy to achieve best patient outcome. HNSCC is heterogeneous in its basis, mechanism, and behaviour, and its biomarkers are considered greatly important in identifying the tumorigenesis mechanism that is involved in therapy resistance to increase patient survival. Resistance to chemotherapy is a major cause of treatment failure in HNSCC patients; the long-term assessment of a patient’s compliance with chemotherapy is key to overcoming treatment resistance and controlling cancer. FOXM1 is a known oncogene and plays an important role in conferring chemoresistance. The objective of the current study was to investigate candidate approved-chemotherapeutic drugs to inhibit FOXM1 in HNSCC cells in the aim to counteract chemoresistance. Methods: Dose-response assay was performed to investigate the potency of 16 candidate drugs using crystal violet cell viability assay in 11 human cell lines consisting of normal oral keratinocytes, oral fibroblasts, normal skin keratinocytes, premalignant oral buccal mucosa and 7 HNSCC cell lines. The most potent drugs with least toxicity towards normal control cells were selected to investigate their effect on FOXM1 gene expression using reverse transcription quantitative PCR. Results: Vincristine, lanatoside A and topotecan were found to be the most potent drugs with least toxicity across the 11 cell lines. Lanatoside A was the only effective drug for a paclitaxel resistant cell line (CaLH2-PTX). All three drugs significantly suppressed FOXM1 gene expression levels in all 7 HNSCC cell lines. Conclusion: This study identified 3 existing candidate approved chemotherapeutic drugs demonstrating potent anti-proliferation effects against a panel of HNSCC cell lines and with low toxicity towards normal cells. Further investigations are needed to understand their mechanisms and their effects on FOXM1 in HNSCC cells.7 0