Related Experiment Video
Updated: Feb 2, 2026

Evaluation of the Spatial Distribution of γH2AX following Ionizing Radiation
Published on: August 7, 2010
Effects of FOXM1 inhibition and ionizing radiation on melanoma cells
Vivienne S Lee1, Lucinda S McRobb1, Vaughan Moutrie2
1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
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.
Insights
Siomycin A effectively reduces metastatic melanoma growth, death, and migration. However, combining this FOXM1 inhibitor with radiation therapy did not enhance treatment efficacy in this cell line.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Metastatic melanoma is often resistant to conventional treatments.
- Forkhead box M1 (FOXM1) is a key regulator in cell proliferation and survival.
- Targeted therapies combined with radiation show promise for improved efficacy.
Purpose of the Study:
- To investigate the efficacy of Siomycin A (SIOA), a FOXM1 inhibitor, alone and in combination with radiation.
- To assess the impact on growth, apoptosis, and migration in metastatic melanoma cells (SK-MEL-28).
Main Methods:
- Utilized a metastatic melanoma cell line (SK-MEL-28) overexpressing FOXM1.
- Administered Siomycin A (SIOA) at various concentrations.
- Applied single doses of ionizing radiation (0-40 Gy).
- Assessed apoptosis, proliferation, and migration (scratch wound assay).
Main Results:
- SIOA alone potently inhibited melanoma cell proliferation and migration.
- SIOA induced apoptosis at concentrations >1 µM, reducing FOXM1 and BCL2 protein levels.
- Ionizing radiation inhibited growth and migration but did not significantly induce cell death.
- SIOA pretreatment did not sensitize melanoma cells to radiation therapy.
Conclusions:
- Siomycin A is an effective single agent for inducing cell death and inhibiting migration in metastatic melanoma cells with constitutive FOXM1 expression.
- Combining Siomycin A with radiation therapy may not offer additional therapeutic benefits in this specific melanoma model.
Related Concept Videos
Biological Effects of Radiation
Ionization Energy
Feedback Inhibition
Radiation: Applications
The average...
Buffer Effectiveness
The buffer capacity is the amount of acid or base that can be added to a given volume...
Absorption of Radiation

