Date of Award
Master of Science (MS)
Background: Lung cancer is the leading cause of cancer related death for both men and women. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer with a 15% five-year survival rate. Current treatment options have serious side effects creating the need for alternative treatments. Methionine restriction (MR) has shown anti-tumor effects on various cancer cells, but the mechanisms involved in NSLCLC is unclear. The purpose of this study is to determine the anti-tumor effects of MR on NSCLC cells through the beta-catenin pathway.
Objective: The purpose of this study is to determine the anti-tumor effects of MR on NSCLC cells through the beta-catenin pathway.
Methods: Human NSCLC cell lines, A549 and H520 were obtained from ATCC and treated in the presence of normal or MR media (95% methionine restriction). After 48 hours of incubation, cell viability was determined by the alamar blue assay and a clonogenic assay was performed separately. A549 and H520 were treated for 24, 48, and 72 hours and cultured for harvest. Cell cycle was analyzed by measuring the DNA content of each cells determined using flow cytometry and western blot was performed using the antibodies β-actin, β-catenin, phospho β-catenin, and PARP. In order to investigate the potential molecular mechanism of MR on NSCLC cell, a human phospho-kinase array was performed.
Results: MR significantly inhibits the cell proliferation in A549 and H520 cells after 48 hours. MR induces cell cycle arrest in G1 compared with the control after 24 hours of treatment. Protein expressions of PARP and phospho β-catenin are reduced in response to MR. The protein kinase array indicates MR exerts its anti-cancer effects by reducing phosphorylation of beta-catenin.
Conclusion: Our results show MR has an inhibitory effect on the cell proliferation and colony formation of A549 and H520 cancer cell lines. Cell cycle arrest and reduced phosphorylated β-catenin provides insight into how methionine metabolism inhibits lung cancer development and progression. Further in vivo studies are needed in order to testify the efficacy of MR as a cancer prevention approach for NSCLC.
Hobson, Katherine, "METHIONINE RESTRICTION INHIBITS NON-SMALL CELL LUNG CANCER GROWTH BY TARGETING THE BETA-CATENIN PATHWAY." Thesis, Georgia State University, 2018.