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- Title
Effects of FOXM1 inhibition and ionizing radiation on melanoma cells.
- Authors
Lee, Vivienne S.; McRobb, Lucinda S.; Moutrie, Vaughan; Santos, Estavam D.; Siu, Timothy L.
- Abstract
Metastatic melanoma can be highly refractory to conventional radiotherapy and chemotherapy but combinatorial-targeted therapeutics are showing greater promise on improving treatment efficacy. Previous studies have shown that knockdown of Forkhead box M1 (FOXM1) can sensitize various tumor types to radiation-induced cell death. The effect of combining radiation with a small molecule FOXM1 inhibitor, Siomycin A, on growth, death and migration of a metastatic melanoma cell line (SK-MEL-28) that overexpresses this pleiotropic cell cycle regulator was investigated. Siomycin A (SIOA) was found to be a strong inducer of apoptosis, and inhibitor of proliferation and migration in a scratch wound assay in this cell line. Induction of apoptosis occurred at concentrations >1 µM in association with reductions in the constitutive FOXM1 and anti-apoptotic B-cell lymphoma 2 protein levels found in these cells. Single doses of ionizing radiation (0–40 Gy) delivered by linear accelerator caused inhibition of growth and migration without significant induction of cell death. Pretreatment with SIOA did not increase the sensitivity of this melanoma cell line to radiation as observed in other tumor types. These data confirm that as a single agent, SIOA is an effective inducer of cell death and inhibitor of migration in metastatic melanoma cells expressing constitutive FOXM1. In combination with radiation, SIOA pre-treatment, however, may not be of added benefit.
- Subjects
MELANOMA; IONIZING radiation; CANCER chemotherapy; CELL cycle; CELL death
- Publication
Oncology Letters, 2018, Vol 16, Issue 5, p6822
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2018.9482