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Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis
The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218039/ https://www.ncbi.nlm.nih.gov/pubmed/30395606 http://dx.doi.org/10.1371/journal.pone.0206467 |
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author | Villanueva, Paulina J. Martinez, Alberto Baca, Sarah T. DeJesus, Rebecca E. Larragoity, Manuel Contreras, Lisett Gutierrez, Denisse A. Varela-Ramirez, Armando Aguilera, Renato J. |
author_facet | Villanueva, Paulina J. Martinez, Alberto Baca, Sarah T. DeJesus, Rebecca E. Larragoity, Manuel Contreras, Lisett Gutierrez, Denisse A. Varela-Ramirez, Armando Aguilera, Renato J. |
author_sort | Villanueva, Paulina J. |
collection | PubMed |
description | The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of four leukemia/lymphoma cell lines with promising values of 3.3 to 3.5. One breast cancer and one leukemia cell line were tested further in order to determine the likely mode of action of PND. PND was found to consistently elicit phosphatidylserine externalization, mitochondrial depolarization, and DNA fragmentation, in both the triple negative MDA-MB-231 breast cancer and HL-60 leukemia cell lines. In addition, PND treatment altered cell cycle progression in both cancer cells. Subsequent DNA mobility-shift assays, UV-Visible spectroscopic titrations, and circular dichroism (CD) experiments revealed that PND intercalates with DNA. The findings presented in this study indicates that PND induces apoptosis and interfered with cell cycle progression of cancer cell lines and these results indicate that this drug has the potential as a repurposed drug for cancer therapy. |
format | Online Article Text |
id | pubmed-6218039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62180392018-11-19 Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis Villanueva, Paulina J. Martinez, Alberto Baca, Sarah T. DeJesus, Rebecca E. Larragoity, Manuel Contreras, Lisett Gutierrez, Denisse A. Varela-Ramirez, Armando Aguilera, Renato J. PLoS One Research Article The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of four leukemia/lymphoma cell lines with promising values of 3.3 to 3.5. One breast cancer and one leukemia cell line were tested further in order to determine the likely mode of action of PND. PND was found to consistently elicit phosphatidylserine externalization, mitochondrial depolarization, and DNA fragmentation, in both the triple negative MDA-MB-231 breast cancer and HL-60 leukemia cell lines. In addition, PND treatment altered cell cycle progression in both cancer cells. Subsequent DNA mobility-shift assays, UV-Visible spectroscopic titrations, and circular dichroism (CD) experiments revealed that PND intercalates with DNA. The findings presented in this study indicates that PND induces apoptosis and interfered with cell cycle progression of cancer cell lines and these results indicate that this drug has the potential as a repurposed drug for cancer therapy. Public Library of Science 2018-11-05 /pmc/articles/PMC6218039/ /pubmed/30395606 http://dx.doi.org/10.1371/journal.pone.0206467 Text en © 2018 Villanueva et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Villanueva, Paulina J. Martinez, Alberto Baca, Sarah T. DeJesus, Rebecca E. Larragoity, Manuel Contreras, Lisett Gutierrez, Denisse A. Varela-Ramirez, Armando Aguilera, Renato J. Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title | Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title_full | Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title_fullStr | Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title_full_unstemmed | Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title_short | Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
title_sort | pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218039/ https://www.ncbi.nlm.nih.gov/pubmed/30395606 http://dx.doi.org/10.1371/journal.pone.0206467 |
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