Document Type

Thesis

Date of Award

5-2024

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

Committee Chairperson

Mario Hollomon

Committee Member 1

Erica Cassimere

Committee Member 2

Hector Miranda

Committee Member 3

Jahmario Williams

Keywords

AS1842856, cell cycle, FOXO1 inhibition, osteosarcoma

Abstract

Forkhead box class O (FOXO)-1 transcription factor controls cell proliferation, apoptosis, oxidative stress, and other cellular activities; FOXO1 has also been implicated in cell cycle regulation. This research project aims to determine the contribution of FOXO1 to cell cycle regulation and response to anticancer drug treatment in osteosarcoma. Osteosarcoma is the most common bone cancer, with most cases occurring in people younger than 30 years old. The study explores the impact of FOXO1 inhibitor AS1842856 on the cytotoxic effects of anticancer drugs in CCHOSD, Hos, and LM7 osteosarcoma (OGS) cell lines. Following chemical inhibition of FOXO1 and anticancer drug treatment, cell cycle and anticancer drug-induced cell death were determined using cell cycle analysis. It was observed that OGS cell lines do not naturally produce p21. However, FOXO1 suppression led to a G2/M cell cycle phase arrest, coinciding with an upsurge in p21 expression in CCHOSD and LM7 cell lines. FOXO1 inhibition increased p16, p21, and p27 levels in CCHOSD cells, elevated p21 expression in LM7 cells, and reduced expression of p27 in LM7 cells. Interestingly, inhibition of FOXO1 counteracted cell death induced by anticancer drugs. The data generated in this project indicated that baseline expression of cell cycle inhibitors varies among OGS cell lines and influences cell cycle arrest differently. Additionally, findings suggest that the reversal of anticancer drug-induced cell death by FOXO1 inhibition is associated with induced arrest in the cell cycle.

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