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Purpose: Aconitine, a potent alkaloid from Aconitum plants, has shown promising anticancer properties. The aim of the study is to investigate the effects of aconitine on lateral migration, and matrix metalloproteinase (MMP) activity in MDA-MB-231 triple-negative breast cancer cells. Material and Methods: A WST-1 viability assay was conducted to determine the effect of aconitine on the viability of MDA-MB-231 cells. Following treatment with non-cytotoxic doses of aconitine, lateral migration was evaluated through wound healing assays. Additionally, gelatin zymographywas conducted to analyze MMP-2 and MMP-9 activity and secretion levels. Results: Aconitine concentrations up to 200 pM did not significantly affect cell viability for up to 72 hours, whereas higher doses (400-600 pM) reduced viability in a time-dependent manner. Aconitine at 200 pM showed a trend towards decreased lateral motility, with a significant reduction at 9 hours post-treatment. Gelatin zymography revealed no alterations in MMP-2 and MMP-9 activity or secretion levels following aconitine treatment. Conclusion: Aconitine demonstrates limited efficacy in modulating the migratory capacity of MDA-MB-231 cells and does not affect gelatinase activity. Further investigation into underlying mechanisms is necessary, potentially leading to novel therapeutic strategies for triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Summary: Background: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen‐activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP‐1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. Objectives: In this study, we investigated the effects of melatonin on UVA‐irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time‐dependent manner which have not been clearly elucidated yet. Methods: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub‐cytotoxic dosage (20 J/cm2) after pretreatment with melatonin (1 μmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. Results: Our results clearly show that melatonin decreases UVA‐induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP‐1 signal transduction pathway and production of matrix metalloproteinases in a time‐dependent manner. Conclusion: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation. [ABSTRACT FROM AUTHOR]

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