Melatonin Enhances Anti-tumoral Effects of Menadione on Colon Cancer Cells.
Colon cancer
antiproliferative effects
melatonin
menadione
oxidative stress
wound healing assay
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2022
2022
Historique:
received:
31
03
2021
revised:
11
07
2021
accepted:
07
10
2021
pubmed:
9
12
2021
medline:
29
6
2022
entrez:
8
12
2021
Statut:
ppublish
Résumé
Colon cancer is one of the most important causes of death in the 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. The objective of this study is to determine the antitumoral action of the combination MEN and MEL on colon cancer cells. Caco-2 cells were employed to evaluate the effects of both compounds, used alone or combined, on cellular growth/morphology, oxidative and nitrosative stress, and cell migration. MEN plus MEL dramatically reduced cell proliferation in a time and dose-dependent manner. The antiproliferative 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 process was delayed. Also, changes in nuclear morphology consistent with cell death were observed. The enhanced effect of simultaneous use of MEN and MEL on Caco-2 cells suggests that this combined action may have therapeutic potential as an adjuvant on intestinal cancer acting in different oncogenic pathways.
Sections du résumé
BACKGROUND
Colon cancer is one of the most important causes of death in the 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
The objective of this study is to determine the antitumoral action of the combination MEN and MEL on colon cancer cells.
METHODS
Caco-2 cells were employed to evaluate the effects of both compounds, used alone or combined, on cellular growth/morphology, oxidative and nitrosative stress, and cell migration.
RESULTS
MEN plus MEL dramatically reduced cell proliferation in a time and dose-dependent manner. The antiproliferative 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 process was delayed. Also, changes in nuclear morphology consistent 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 therapeutic potential as an adjuvant on intestinal cancer acting in different oncogenic pathways.
Identifiants
pubmed: 34875993
pii: ACAMC-EPUB-119277
doi: 10.2174/1871520621666211207141729
doi:
Substances chimiques
Antioxidants
0
Buthionine Sulfoximine
5072-26-4
Vitamin K 3
723JX6CXY5
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2411-2418Informations de copyright
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