In vitro and in silico approaches to unveil the mechanisms underlying the cytotoxic effect of juncunol on human hepatocarcinoma cells
Küçük Resim Yok
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
POLISH ACAD SCIENCES INST PHARMACOLOGY
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: Juncunol is a phenanthrene isolated from the halophyte species Juncus acutus, with selective cytotoxic activity towards human hepatocarcinoma (HepG2) cells. However, its mechanism of action is unknown. Methods: The in vitro cytotoxic mechanism of juncunol was evaluated on HepG2 cells through several methods to elucidate its potential to induce apoptotic features, decrease mitochondrial membrane potential, promote internal ROS production and influence cell cycle. We also report its haemolytic activity on human erythrocytes and in silico DNA-binding studies. Results: Juncunol induced an increase in the number of apoptotic cells in a concentration-dependent manner, accompanied by a decrease in the mitochondrial membrane potential. Nosignificant differences were observed in production of reactive oxygen species (ROS). Moreover, juncunol application at the IC50 value significantly induced cell cycle arrest in the G0/G1 phase comparatively to the control group. No significant haemolysis was detected. In silico studies indicate that juncunol seems to bind between GC base pairs. Conclusion: Juncunol reduced HepG2 cells proliferation through the induction of apoptotic cellular death, in a concentration-dependent manner. Apoptosis induction seems to be related with a decrease of the mitochondrial membrane potential but not with ROS production. Juncunol had no haemolytic activity and may act as a DNA intercalator. Our data suggests juncunol as a suitable candidate for more detailed studies, including in vivo experiments, in order to completely characterize its mode of action. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
Açıklama
Anahtar Kelimeler
Apoptosis, Mitochondrial membrane potential, Reactive oxygen species, Cell cycle, Haemolysis, Flow cytometry, DNA binding
Kaynak
PHARMACOLOGICAL REPORTS
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
70
Sayı
5
