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Melatonin Enhances Anti-tumoral Effects of Menadione on Colon Cancer Cells

Alejandro Collin1, Romina Kohan1,2, Nori Tolosa de Talamoni1

  • 1Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba (UNC), Instituto de Investigaciones en Ciencias de la Salud (INICSA), CONICET-UNC, Córdoba, Argentina.

Anti-Cancer Agents in Medicinal Chemistry
|December 8, 2021
PubMed
Abstract

Insights

Menadione (MEN) and melatonin (MEL) combination significantly inhibited colon cancer cell growth and migration. This dual-action therapy shows potential for treating intestinal cancers by targeting multiple pathways.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Colon cancer remains a leading global cause of mortality, necessitating novel therapeutic strategies, particularly for resistant forms.
  • Previous research indicated that menadione (MEN), buthionine sulfoximine, and calcitriol combinations enhance tumor cell sensitivity by altering oxidative status.
  • Melatonin (MEL), a circadian rhythm hormone, exhibits antioxidant and anti-apoptotic properties at low doses and inhibits cancer cell growth at high doses.

Purpose of the Study:

  • To investigate the combined antitumoral effects of menadione (MEN) and melatonin (MEL) on colon cancer cells.
  • To assess the impact of MEN and MEL on cellular proliferation, morphology, oxidative stress, and migration in colon cancer models.

Main Methods:

  • Caco-2 colon cancer cells were utilized to evaluate the effects of MEN and MEL, both individually and in combination.
  • Assessed were cellular growth, morphology, oxidative and nitrosative stress markers, and cell migration.
  • Evaluated time- and dose-dependent effects of the MEN and MEL combination.

Main Results:

  • The combination of MEN and MEL significantly reduced Caco-2 cell proliferation in a time- and dose-dependent manner, with effects observed after 48 hours.
  • The combined treatment altered cellular oxidative status, increasing superoxide anion content and catalase activity while inducing reactive nitrogen species formation.
  • Significant delays in cell migration and observable changes in nuclear morphology indicative of cell death were noted.

Conclusions:

  • The synergistic effect of combined MEN and MEL on Caco-2 cells suggests significant therapeutic potential.
  • This combination may serve as an effective adjuvant therapy for intestinal cancers.
  • The dual-action approach targets multiple oncogenic pathways, offering a promising strategy for colon cancer treatment.
Keywords:
Colon cancerantiproliferative effectsmelatoninmenadioneoxidative stresswound healing assay

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