Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis.
Paulina J VillanuevaAlberto MartinezSarah T BacaRebecca E DeJesusManuel LarragoityLisett ContrerasDenisse A GutierrezArmando Varela-RamirezRenato J AguileraPublished in: PloS one (2018)
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.
Keyphrases
- cell cycle
- cell proliferation
- acute myeloid leukemia
- cell cycle arrest
- cancer therapy
- circulating tumor
- oxidative stress
- bone marrow
- single molecule
- cell free
- induced apoptosis
- squamous cell carcinoma
- anti inflammatory
- breast cancer cells
- cell death
- drug induced
- risk assessment
- papillary thyroid
- high throughput
- molecular docking
- adverse drug
- pi k akt
- molecular dynamics simulations
- replacement therapy
- lymph node metastasis
- human health