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.
Highlights
Because there is no current effective treatment for metastatic melanoma and the average survival time is only 6 to 10 months [1,2], one way to control for malignancy is via prevention
Liu et al [5] found that this compound induced tumor cell differentiation by modulating the expression of genes implicated in tumor metastasis and immunogenicity in cultured human melanoma cells
The IC50 in the NGM cells was not reached, and the cell growth was very similar among the different treatment groups compared to the control cells
Summary
Because there is no current effective treatment for metastatic melanoma and the average survival time is only 6 to 10 months [1,2], one way to control for malignancy is via prevention. Several studies have shown that the consumption of vegetables and fruits decreases the risk of many malignancies [5,6,7] and can protect against cancers [8,9,10]. Natural products have been well recognized as a source of drugs, and some plant extracts and compounds that are isolated from medicinal plants have been identified for their anti-cancer activities [11,12]. One anti-tumoral compound isolated from several plant-derived products is cinnamic acid. Cinnamic acid and its associated compounds can be found in coffee, apples, citric fruits, vegetable oils, propolis and wine. Cinnamic acid has a long history of human use as a component of plant-derived scents and flavoring agent [13]. Liu et al [5] found that this compound induced tumor cell differentiation by modulating the expression of genes implicated in tumor metastasis and immunogenicity in cultured human melanoma cells
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