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Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis.

التفاصيل البيبلوغرافية
العنوان: Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis.
المؤلفون: Paulina J Villanueva, Alberto Martinez, Sarah T Baca, Rebecca E DeJesus, Manuel Larragoity, Lisett Contreras, Denisse A Gutierrez, Armando Varela-Ramirez, Renato J Aguilera
المصدر: PLoS ONE, Vol 13, Iss 11, p e0206467 (2018)
بيانات النشر: Public Library of Science (PLoS), 2018.
سنة النشر: 2018
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC6218039?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0206467
URL الوصول: https://doaj.org/article/8e1041405ca847759a40a39062954a98
رقم الأكسشن: edsdoj.8e1041405ca847759a40a39062954a98
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0206467