A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

The biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from Caesalpinia spinosa was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity.We found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC50) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin.Our results suggest that a natural fraction extracted from Caesalpinia spinosa in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia.Caesalpinia spinosa is a shrub commonly named dividivi. It is acknowledged to have antimicrobial and antioxidant activity, and is traditionally known for its antitumor activity [1]. An ethanol extract from the fruit of C.spinosa has been proven to have antimicrobial activity against gram-positive and gram-negative bacteria, probably due to the presence of hydrolysable tannins in the fruits [2]. Hydrolysable tannins are a group of gallic acid esters associated with polyols (glucose, glucitol, shikimic acid, quinic acid and quercitol, among others), where the galloyl groups can be further cross-linked by etherification or oxidation to form complex structures. The gallotannins (gallic acid esters) are the simplest hydrolysable tannins, were 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose [