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

COLLIN, ALEJANDRO; KOHAN, ROMINA; TOLOSA DE TALAMONI, NORI; PICOTTO, GABRIELA

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Año: 2021

1871-5206

Background: Colon cancer is one of the most important causes of death in entire world. New pharmacological strategies are always needed, especially in resistant variants of this pathology. We have previously reported that drugs such as menadione (MEN), D, L-buthionine-S,R-sulfoximine or calcitriol, used in combination, enhanced cell sensibility of breast and colon tumour models, due to their ability to modify the oxidative status of the cells. Melatonin (MEL), a hormone regulating circadian rhythms, has anti-oxidant and anti-apoptotic properties at low concentrations, while at high doses it has been shown to inhibit cancer cell growth. Objective: To determine the antitumoral action of the combination MEN and MEL on Caco-2 cells. Materials and Methods: We employed colon cancer cells to evaluate the effects of both compounds used alone and combined, on cellular growth/morphology, oxidative and nitrosative stress, and evaluation of cell migration. Results: MEN plus MEL dramatically reduced cell proliferation in a time and dose-dependent manner. The anti-proliferative effects began at 48 h. At the same time, the combination modified the content of superoxide anion, induced the formation of reactive nitrogen species and enhanced catalase activity. Cell migration was delayed and changes in nuclear morphology compatible with cell death were observed. Conclusion: The enhanced effect of simultaneous use of MEN and MEL on Caco-2 cells, suggests that this combined action may have a therapeutic potential as adjuvant on intestinal cancer acting in different oncogenic pathways.