Nanocytotoxicity: Violacein and Violacein-Loaded Poly (<I>D</I>, <I>L</I>-lactide-co-glycolide) Nanoparticles Acting on Human Leukemic Cells

Potential applications of violacein: a microbial pigment

“…Nanospheres were prepared from biodegradable polymers, such as poly(D,L-lactide-co-glycolide)/ Pluronic F-68/polyvinyl alcohol by the modified method of nano-precipitation with diffusion-evaporation of solvent with excellent antitumoral properties (Durán and De Azevedo, 2004). Similar results in leukemia cell cultures were found for violacein-loaded poly(D,L-lactide-co-glycolide) nanoparticles (Melo et al, 2009) and for b-cyclodextrin-alkylthiol derivatives capping gold nanoparticles complexed with violacein Gimenez et al, 2005).…”

“…Studies using a panel of tumor cell lines from the National Cancer Institute (USA) revealed that purified violacein exhibited best activities against MOLT-4 leukemia, NCI-H460 non-small-cell lung cancer, and KM12 colon-cancer cell lines, with GI 50 (the concentration inhibiting net cell growth by 50%) values in the range 0.01-0.02 lg/ml (0.03-0.06 lM) (Melo et al, 2000). These results stimulated research to investigate its potential as an antitumor agent and the mechanisms of action in cell lines from different histological origins Saraiva et al, 2004;Ferreira et al, 2004;De Carvalho et al, 2006;Kodach et al, 2006;Melo et al, 2009;Bromberg et al, 2010). Furthermore, these studies indicated that cytotoxicity occurs with signs of apoptosis, even though specific signaling pathways were activated depending on the cell line.…”

Antitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein

“…The increased biological activity of violacein loaded in nanoparticles has been demonstrated in previous works either with tumoral cells 26 or Staphylococci strains 27 and the addition of derivatives of ascorbic acid on external surface of nanoparticles had been shown to increase the efficiency of dehydrocrotonin loaded in PLGA nanoparticles with a protein mediated uptake mechanism and a shunt of cell death mechanism to receptor-mediated pathways. 29 However, an unexpected observation was reached, since free ascorbic acid exhibits a buffering effect in violacein-mediated toxicity, while the addition of ascorbic acid on the external surface of PLGA nanoparticles loading violacein actually promotes an improvement of the toxicity of this compound.…”

“…25,26 Briefly, PLGA 50:50 and violacein were dissolved in acetone at concentrations of 1.2% and 0.5% (W/V). respectively.…”

“…29 In all experiments with encapsulated violacein, the final concentration of nanoparticles was maintained constant by addition of a complementary amount of blank. Cell viability was determined by MTT reduction assay and the inhibitory concentration for 50% of the cells (IC 50 ) was standardized as a 26 In order to verify whether free ascorbic acid has any buffering effect in free violacein-mediated toxicity, cells were exposed to free violacein at IC 50 values and a concentration of ascorbic acid equivalent to the total amount of this compound recovered from NP-AA. Also, in line with previous literature, 30 no decrease in the viability of HL-60 cells was observed when the cells were exposed to free ascorbic acid in concentrations below 10 µM (data not shown).…”