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Article Publish Status: FREE
Abstract Title:

Selective Cytotoxicity of Piperine Over Multidrug Resistance Leukemic Cells.

Abstract Source:

Molecules. 2021 Feb 10 ;26(4). Epub 2021 Feb 10. PMID: 33578817

Abstract Author(s):

Julia Quarti, Daianne N M Torres, Erika Ferreira, Raphael S Vidal, Fabiana Casanova, Luciana B Chiarini, Eliane Fialho, Vivian M Rumjanek

Article Affiliation:

Julia Quarti

Abstract:

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 of PARP-1 in MDR FEPS cells. We conclude that piperine targets selectively MDR cells, inducing CS, through a mechanism that might be dependent or not on P-gp.

Study Type : In Vitro Study

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