Effects of FOXM1 inhibition and ionizing radiation on melanoma cells

Vivienne S. Lee, Lucinda S. McRobb, Vaughan Moutrie, Estavam D. Santos, Timothy L. Siu

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages6822-6830
Number of pages9
JournalOncology Letters
Volume16
Issue number5
DOIs
Publication statusPublished - 1 Nov 2018

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Ionizing Radiation
Melanoma
Cell Death
Radiation
Cell Line
Apoptosis
Particle Accelerators
Radiation Effects
B-Cell Lymphoma
Growth
Helper-Inducer T-Lymphocytes
Neoplasms
Cell Cycle
Radiotherapy
siomycin A
Drug Therapy
Wounds and Injuries
Therapeutics
Proteins

Cite this

Lee, Vivienne S. ; McRobb, Lucinda S. ; Moutrie, Vaughan ; Santos, Estavam D. ; Siu, Timothy L. / Effects of FOXM1 inhibition and ionizing radiation on melanoma cells. In: Oncology Letters. 2018 ; Vol. 16, No. 5. pp. 6822-6830.
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Effects of FOXM1 inhibition and ionizing radiation on melanoma cells. / Lee, Vivienne S.; McRobb, Lucinda S.; Moutrie, Vaughan; Santos, Estavam D.; Siu, Timothy L.

In: Oncology Letters, Vol. 16, No. 5, 01.11.2018, p. 6822-6830.

Research output: Contribution to journalArticleResearchpeer-review

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