Gallic Acid Derivatives Induce Apoptosis on Melanona Cell Line.
Claudriana Locatelli 1, 2 , Márcio Fritzen 2, Maria Claudia Santos Silva 3, Paulo César Leal 4, Rosendo Augusto Yunes 4, Ricardo Nunes 4, Tania Beatriz Creczynsk Pasa 2.
1 Universidade do Contestado – Curso de Farmácia – UnC; 2 Departamento de Ciências Farmacêuticas – Universidade Federal de Santa Catariana – UFSC; 3 Departamento de Análises Clínicas – Universidade Federal de Santa Catarina – UFSC; 4Departamento de Química - Universidade Federal de Santa Catarina – UFSC.
The gallic acid and its derivatives are a naturally phenolics acids that present a wide variety biological actions. Epidemiological studies indicate that a phenolic compounds rich diet reduces many pathologies risks, as atherosclerosis, neurodegenetarives diseases, cancer and others. However, the great interest has been employed in anti-cancer studies. Some works have demonstrated anti-cancer activity for lauril, methyl and propyl-gallate; they promoted apoptosis in tumor cell lines and liymphocyte proliferation inhibition. Chemical alterations at gallic acid molecule may modifie the pharmacokinetic and pharmacodinamic proprierties, altering the solubility and the partition coefficient (P Log), consequently the biological properties. The new structures show different interactions with macromolecules and lipid membranes permeability. Therefore in this study, we investigate the influence of lipophilicity of galic acid n-alquil-esters derivates on cytotoxicity for B16F10 melanoma cells. B16F10 cells were incubated for 24 h with gallic acid or with n-alquil-esters (hexyl, heptyl, octyl, decyl, undecyl, dodecyl, tetradecyl and hexadecyl) in a range of 10 to 100 mM. Cell viability was monitored through MTT assay, the apoptosis was analyzed by DNA fragmentation in 1,5% agarose gel eletrophoresis. All compounds induced cytotoxic effects on melanoma cells in a concentration dependent way. The higher cytotoxicity were observed with decyl and tetradecyl gallate witch promoted about 70 ± 3% and 80 ± 1% of cell death respectively at 100 mM, the cell viability was significantly smaller than that of the control (cells without treatment). The IC50 values obtained are in micromolar range, between 66 mM and 150 mM for octyl and hexadecyl gallate respectively. All compounds caused DNA fragmentation at 100 mM after 24 h of incubation. The results suggest that n-alquil-esters of gallic acid are able to promote cell death through apoptosis and it is dependent on the carbonic chain size. It was observed that decyl and tetradecyl gallate were more potent, being possible to conclude that there is a limit of compounds P Log for anticancer activity.
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