Farrerol suppresses the progression of laryngeal squamous cell carcinoma via the mitochondria-mediated pathway.

Abstract

PURPOSE:

In the context of well-known inhibitory effects of Farrerol on the invasion of lung squamous cell carcinoma cells, the unexplored effect and regulatory mechanism of Farrerol on laryngeal squamous cell carcinoma (LSCC) emerged as the target in this study.

METHODS:

After treatment with Farrerol alone, or together with MitoTempo, the viability, apoptosis, cell cycle distribution, migration, and invasion of LSCC cells were measured using MTT, flow cytometry, wound-healing, and transwell assays, respectively. Meanwhile, the levels of cytochrome C (Cyt C), Cleaved caspase-3/9, Cyclin D1, E-cadherin, N-cadherin, and Vimentin in LSCC cells were evaluated by Western blot; the reactive oxygen species (ROS) formation intensity and the disruption of mitochondrial membrane potential (MMP) of LSCC cells were assessed using flow cytometry; and the effect of Farrerol on xenograft tumor formation was evaluated in animal experiment.

RESULTS:

Farrerol (10, 20, 50 μM) inhibited the viability, proliferation, cell cycle progression, migration and invasion, but promoted apoptosis, ROS formation intensity and disruption of MMP of LSCC cells. Moreover, Farrerol up-regulated Cyt C (in the cytoplasm), Cleaved caspase-3/9 and E-cadherin levels, but down-regulated Cyclin D1, N-cadherin and Vimentin levels in LSCC cells. Additionally, we uncovered that MitoTempo reversed the promoting effects of Farrerol on ROS formation intensity, apoptosis, and Cyt C and Cleaved caspase-3/9 levels in LSCC cells, while improving the disruption of MMP in Farrerol-treated LSCC cells. Also, Farrerol lessened the volume and weight of mice tumors.

CONCLUSIONS:

Farrerol suppressed the migration, invasion, and induced the apoptosis of LSCC cells via the mitochondria-mediated pathway.

• Authors: Tingting Zhang, Hui Liu, Min Liu, Chunhong Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 913 Pg. 174636 (Dec 15 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34801529 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Chromones
• MitoTEMPO
• Organophosphorus Compounds
• Piperidines
• Reactive Oxygen Species
• farrerol

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects, genetics)
• Chromones (pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Laryngeal Neoplasms (drug therapy, genetics, pathology)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mitochondria (drug effects, metabolism)
• Neoplasm Invasiveness (pathology, prevention & control)
• Organophosphorus Compounds (pharmacology)
• Piperidines (pharmacology)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Squamous Cell Carcinoma of Head and Neck (drug therapy, genetics, pathology)
• Up-Regulation (drug effects)
• Xenograft Model Antitumor Assays