Molecules, Vol. 26, Pages 934: Selective Cytotoxicity of Piperine Over Multidrug Resistance Leukemic Cells

Molecules, Vol. 26, Pages 934: Selective Cytotoxicity of Piperine Over Multidrug Resistance Leukemic Cells Molecules doi: 10.3390/molecules26040934 Authors: Julia Quarti Daianne N. M. Torres Erika Ferreira Raphael S. Vidal Fabiana Casanova Luciana B. Chiarini Eliane Fialho Vivian M. Rumjanek Multidrug resistance (MDR) is the main challenge in the treatment of chronic myeloid leukemia (CML), and P-glycoprotein (P-gp) overexpression is an important mechanism involved in this resistance process. However, some compounds can selectively affect MDR cells, inducing collateral sensitivity (CS), which may be dependent on P-gp. The aim of this study was to investigate the effect of piperine, a phytochemical from black pepper, on CS induction in CML MDR cells, and the mechanisms involved. The results indicate that piperine induced CS, being more cytotoxic to K562-derived MDR cells (Lucena-1 and FEPS) than to K562, the parental CML cell. CS was confirmed by analysis of cell metabolic activity and viability, cell morphology and apoptosis. P-gp was partially required for CS induction. To investigate a P-gp independent mechanism, we analyzed the possibility that poly (ADP-ribose) polymerase-1 (PARP-1) could be involved in piperine cytotoxic effects. It was previously shown that only MDR FEPS cells present a high level of 24 kDa fragment of PARP-1, which could protect these cells against cell death. In the present study, piperine was able to decrease the 24 kDa fragment...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research