Kohan et al, 2026. Oxidative stress-driven antiproliferative effects of menadione and calcitriol combination in Caco-2 cells.

Description

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic approaches, particularly for treatment-resistant disease. Redox-based strategies may selectively target tumor cells by overwhelming their antioxidant defences. Menadione (MEN), a redox-cycling naphthoquinone, promotes reactive oxygen species (ROS) generation that also has anticancer effects, whereas calcitriol (1,25D) exerts pleiotropic antitumor effects that include induction of apoptosis, antiproliferative effects and inhibition of invasion and metastasis among others. This study aimed to evaluate the antiproliferative and cytotoxic activity of the MEN+1,25D combination in human Caco-2 cells, and to elucidate the potential involvement of oxidative stress in mediating these effects. MEN+1,25D markedly inhibited cell proliferation in a time- and dose-dependent manner, reducing viability by approximately 80% after 96 h. The combined treatment also impaired migration, induced G2/M cell-cycle arrest, and promoted apoptotic and necrotic cell death associated with increased ROS production and membrane damage. Inhibition of autophagy did not significantly restore viability, whereas antioxidants partially rescued cell survival. These findings suggest that MEN+1,25D exerts potent antitumor effects in Caco-2 cells predominantly through oxidative stress-dependent mechanisms, supporting its potential as a promising therapeutic and adjuvant strategy against colon cancer.

Steps to reproduce

These are the results of part of our research work at the National University Cordoba, Argentina

Institutions

• Universidad Nacional de Córdoba

  Cordoba, Córdoba

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