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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells
Evandro Luís de Oliveira Niero1, Gláucia Maria Machado-Santelli
1Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av, Prof, Lineu Prestes, 1524, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
Abstract:
Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.
Insights
Cinnamic acid effectively inhibits melanoma cell growth by inducing apoptosis and DNA damage. While potent against cancer cells, its potential genotoxicity in normal melanocytes requires further study.
Area of Science:
- Pharmacology
- Cell Biology
- Genetics
Background:
- Cinnamic acid derivatives exhibit anticancer properties, including apoptosis induction via DNA damage.
- Melanoma and melanocyte cell lines present distinct responses to cytotoxic agents.
Purpose of the Study:
- To compare the cytotoxic and genotoxic effects of cinnamic acid on human melanoma (HT-144) and melanocyte (NGM) cell lines.
- To investigate the mechanisms of cell death, including DNA synthesis inhibition, nuclear aberrations, and apoptosis.
Main Methods:
- Cell viability assays (IC50 determination) were performed on HT-144 and NGM cells.
- DNA damage and apoptosis were assessed using BrdU incorporation, nuclear aberration counts, and activated-caspase 3 staining.
- Micronucleation, binucleation, and multinucleation frequencies were analyzed to evaluate genotoxicity.
Main Results:
- Cinnamic acid demonstrated significant cytotoxicity against HT-144 cells (IC50 = 2.4 mM) compared to NGM cells.
- Apoptosis, DNA synthesis inhibition, and nuclear aberrations were observed in HT-144 cells following treatment.
- Increased micronucleation frequency in both cell types indicated genotoxic potential, with milder effects in NGM cells.
Conclusions:
- Cinnamic acid exhibits effective antiproliferative activity against melanoma cells.
- The compound induces apoptosis and DNA damage, leading to cell death in melanoma.
- Potential genotoxicity in normal melanocytes warrants further investigation.
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