4.7 Article

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

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 913, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ejphar.2021.174636

Keywords

Farrerol; LSCC; Cell cycle progression; Invasion; Apoptosis

Funding

  1. [2019-0398]

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Farrerol inhibited the viability, proliferation, cell cycle progression, migration, and invasion, but promoted apoptosis, ROS formation intensity, and disruption of MMP in LSCC cells. Additionally, Farrerol up-regulated Cyt C, Cleaved caspase-3/9, and E-cadherin levels, while down-regulating Cyclin D1, N-cadherin, and Vimentin levels in LSCC cells, suggesting that Farrerol suppressed migration and invasion and induced apoptosis in LSCC cells through the mitochondria-mediated pathway.
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 mu M) 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.

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