{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:22:19Z","timestamp":1768688539363,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["xxx"],"award-info":[{"award-number":["xxx"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/molecules26040934","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T16:12:10Z","timestamp":1613146330000},"page":"934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Selective Cytotoxicity of Piperine over Multidrug Resistance Leukemic Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Julia","family":"Quarti","sequence":"first","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Institute of Nutrition Josu\u00e9 de Castro, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daianne N. M.","family":"Torres","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Nutrition Josu\u00e9 de Castro, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael S.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Casanova","sequence":"additional","affiliation":[{"name":"Institute of Nutrition Josu\u00e9 de Castro, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana B.","family":"Chiarini","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7272-0021","authenticated-orcid":false,"given":"Eliane","family":"Fialho","sequence":"additional","affiliation":[{"name":"Institute of Nutrition Josu\u00e9 de Castro, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian M.","family":"Rumjanek","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.exphem.2016.11.005","article-title":"Preclinical approaches in chronic myeloid leukemia: From cells to systems","volume":"47","author":"Clarke","year":"2017","journal-title":"Exp. 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