Cumulative effects of ciprofloxacin and pilocarpine on cytotoxicity and G0 phase arrest in hepatoma-derived Hep G2 cell line.
Anti-Bacterial Agents
/ administration & dosage
Cell Cycle Checkpoints
/ drug effects
Cell Survival
/ drug effects
Ciprofloxacin
/ administration & dosage
Cytotoxins
/ administration & dosage
Drug Combinations
Hep G2 Cells
Humans
Muscarinic Agonists
/ administration & dosage
Pilocarpine
/ administration & dosage
Resting Phase, Cell Cycle
/ drug effects
Ca2+ homoeostasis
DNA double-strand breaks
cell cycle arrest
combined drug
mitochondrial-dependent apoptosis
synergic effect
Journal
The Journal of pharmacy and pharmacology
ISSN: 2042-7158
Titre abrégé: J Pharm Pharmacol
Pays: England
ID NLM: 0376363
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
12
02
2020
accepted:
23
05
2020
pubmed:
23
6
2020
medline:
23
6
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma-derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca Cells were treated by CPF and/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated. MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF-exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P-Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction. Ciprofloxacin imposed mitochondrial-independent apoptosis while PILO + CPF caused mitochondrial-dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms.
Substances chimiques
Anti-Bacterial Agents
0
Cytotoxins
0
Drug Combinations
0
Muscarinic Agonists
0
Pilocarpine
01MI4Q9DI3
Ciprofloxacin
5E8K9I0O4U
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1383-1393Subventions
Organisme : University of Tabriz
Informations de copyright
© 2020 Royal Pharmaceutical Society.
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