Ivermectin induces cell cycle arrest and apoptosis of HeLa cells via mitochondrial pathway.
Antineoplastic Agents
/ pharmacology
Antiparasitic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Survival
/ drug effects
Female
HeLa Cells
Humans
Ivermectin
/ pharmacology
Membrane Potential, Mitochondrial
/ drug effects
Mitochondria
/ drug effects
Uterine Cervical Neoplasms
/ drug therapy
antimigratory effects
apoptosis
cell cycle arrest
cervical cancer
ivermectin
mitochondrial pathway
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
25
07
2018
revised:
16
09
2018
accepted:
17
09
2018
pubmed:
6
12
2018
medline:
16
4
2019
entrez:
6
12
2018
Statut:
ppublish
Résumé
The aim of study was to investigate the anticancer activities of Ivermectin (IVM) and the possible mechanisms in cells level via cell proliferation inhibition, apoptosis and migration inhibition in model cancer cell HeLa. The MTT assay was used to study the inhibitory effect of IVM on the proliferation of Hela cells, and the cell cycle was analysed by flow cytometry. The neutral comet assay was used to study the DNA damage. The presence of apoptosis was confirmed by DAPI nuclear staining and flow cytometry. Changes in mitochondrial membrane potential and reactive oxygen species (ROS) levels were determined using Rhodamine 123 staining and DCFH-DA staining. Western blot analysis for apoptosis-related proteins was carried out. We use scratch test to analyse the antimigration potential of IVM. Ivermectin can inhibit the viability of HeLa cells significantly. In addition, treatment with IVM resulted in cell cycle arrest at the G1/S phase which partly account for the suppressed proliferation. Typical apoptosis morphological changes were shown in IVM treatment cells including DNA fragmentation and chromatin condensation. At the same time, the results of flow cytometry analysis showed that the number of apoptotic cells increased significantly with the increase of IVM concentration. Moreover, we observed that the mitochondrial membrane potential collapses and the ratio of Bax/Bcl-2 in the cytoplasm increases, which induces cytochrome c release from the mitochondria to the cytoplasm, activates caspase-9/-3 and finally induces apoptosis. We also found that IVM can significantly increase intracellular ROS content. At the same time, we determined that IVM can significantly inhibit the migration of HeLa cells. Our experimental results show that IVM might be a new potential anticancer drug for therapy of human cancer.
Identifiants
pubmed: 30515909
doi: 10.1111/cpr.12543
pmc: PMC6496724
doi:
Substances chimiques
Antineoplastic Agents
0
Antiparasitic Agents
0
Ivermectin
70288-86-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12543Subventions
Organisme : China Postdoctoral Science Foundation
ID : 2017M621393
Organisme : Exploration and Research Fund for Excellent Youth Scholars
ID : 222201814050
Organisme : National Natural Science Foundation of China
ID : 31501674
Informations de copyright
© 2018 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
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