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.

Oncology Letters
|November 9, 2018
PubMed

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.

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